ClinVar Genomic variation as it relates to human health
NM_198253.3(TERT):c.835G>A (p.Ala279Thr)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_198253.3(TERT):c.835G>A (p.Ala279Thr)
Variation ID: 39125 Accession: VCV000039125.37
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5p15.33 5: 1294051 (GRCh38) [ NCBI UCSC ] 5: 1294166 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Jun 9, 2024 Feb 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_198253.3:c.835G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_937983.2:p.Ala279Thr missense NM_001193376.3:c.835G>A NP_001180305.1:p.Ala279Thr missense NR_149162.3:n.914G>A non-coding transcript variant NR_149163.3:n.914G>A non-coding transcript variant NC_000005.10:g.1294051C>T NC_000005.9:g.1294166C>T NG_009265.1:g.5997G>A LRG_343:g.5997G>A LRG_343t1:c.835G>A LRG_343p1:p.Ala279Thr O14746:p.Ala279Thr - Protein change
- A279T
- Other names
- -
- Canonical SPDI
- NC_000005.10:1294050:C:T
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00958 (T)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00921
1000 Genomes Project 0.00958
Trans-Omics for Precision Medicine (TOPMed) 0.01679
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.02123
The Genome Aggregation Database (gnomAD), exomes 0.02249
The Genome Aggregation Database (gnomAD) 0.02258
Exome Aggregation Consortium (ExAC) 0.03611
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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TERT | Little evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2971 | 3413 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign (2) |
criteria provided, single submitter
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Jan 12, 2018 | RCV000032399.16 | |
Benign (8) |
criteria provided, multiple submitters, no conflicts
|
Dec 5, 2016 | RCV000176003.28 | |
Benign (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV000295005.13 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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May 4, 2023 | RCV000391188.14 | |
Benign (1) |
no assertion criteria provided
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- | RCV001269369.9 | |
Benign (2) |
criteria provided, multiple submitters, no conflicts
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Nov 1, 2023 | RCV001534715.11 | |
Benign (1) |
criteria provided, single submitter
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Feb 1, 2024 | RCV002513304.9 | |
Benign (1) |
criteria provided, single submitter
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Dec 24, 2014 | RCV004558283.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Benign
(Dec 05, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000227583.5
First in ClinVar: Jun 28, 2015 Last updated: Oct 02, 2016 |
Number of individuals with the variant: 1
Sex: mixed
|
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Benign
(Dec 24, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Dyskeratosis congenita
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002678574.2
First in ClinVar: Nov 29, 2022 Last updated: Jun 09, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
|
|
Benign
(-)
|
criteria provided, single submitter
Method: clinical testing
|
NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000316923.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
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Benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
|
Dyskeratosis congenita, autosomal dominant 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000452706.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
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Benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Aplastic anemia
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000452708.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Jan 12, 2018)
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criteria provided, single submitter
Method: clinical testing
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Pulmonary fibrosis and/or bone marrow failure, Telomere-related, 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000452707.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
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Benign
(Mar 03, 2015)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV001751657.1
First in ClinVar: Jul 18, 2021 Last updated: Jul 18, 2021 |
|
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Dyskeratosis congenita, autosomal dominant 2
Idiopathic Pulmonary Fibrosis
Explanation for multiple conditions: Uncertain.
The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV000561747.7
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Benign
(Feb 21, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000269873.3
First in ClinVar: May 29, 2016 Last updated: Oct 02, 2016 |
Comment:
Ala279Thr in exon 2 of TERT: This variant is not expected to have clinical signi ficance because it has been identified in 3.0% (255/8580) of … (more)
Ala279Thr in exon 2 of TERT: This variant is not expected to have clinical signi ficance because it has been identified in 3.0% (255/8580) of European American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs61748181). (less)
Number of individuals with the variant: 4
|
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Benign
(Nov 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV004562803.1
First in ClinVar: Feb 20, 2024 Last updated: Feb 20, 2024 |
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Benign
(May 04, 2023)
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criteria provided, single submitter
Method: clinical testing
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Dyskeratosis congenita, autosomal dominant 2
Affected status: yes
Allele origin:
germline
|
Molecular Genetics, Royal Melbourne Hospital
Additional submitter:
Shariant Australia, Australian Genomics
Accession: SCV004812623.1
First in ClinVar: Apr 15, 2024 Last updated: Apr 15, 2024 |
Comment:
European Non-Finnish population allele frequency is 2.81% (rs61748181, 1118/18984 alleles, 30 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, … (more)
European Non-Finnish population allele frequency is 2.81% (rs61748181, 1118/18984 alleles, 30 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1 (less)
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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Breast Cancer
Affected status: yes
Allele origin:
germline
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Center of Medical Genetics and Primary Health Care
Accession: SCV001448729.1
First in ClinVar: Dec 07, 2020 Last updated: Dec 07, 2020 |
|
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001798782.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001808818.1 First in ClinVar: Aug 25, 2021 Last updated: Aug 25, 2021 |
|
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001741333.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001932263.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001955661.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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not provided
(-)
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no classification provided
Method: literature only
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Aplastic anemia
Affected status: not provided
Allele origin:
unknown
|
GeneReviews
Accession: SCV000056055.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Dyskeratosis Congenita and Related Telomere Biology Disorders. | Adam MP | - | 2023 | PMID: 20301779 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=TERT | - | - | - | - |
Text-mined citations for rs61748181 ...
HelpRecord last updated Sep 08, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.