ClinVar Genomic variation as it relates to human health
NM_000051.4(ATM):c.928A>G (p.Ser310Gly)
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.
Uncertain significance(5); Likely benign(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000051.4(ATM):c.928A>G (p.Ser310Gly)
Variation ID: 188110 Accession: VCV000188110.21
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q22.3 11: 108246990 (GRCh38) [ NCBI UCSC ] 11: 108117717 (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 29, 2017 Jun 17, 2024 Mar 3, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000051.4:c.928A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000042.3:p.Ser310Gly missense NM_001351834.2:c.928A>G NP_001338763.1:p.Ser310Gly missense NC_000011.10:g.108246990A>G NC_000011.9:g.108117717A>G NG_009830.1:g.29159A>G LRG_135:g.29159A>G LRG_135t1:c.928A>G LRG_135p1:p.Ser310Gly - Protein change
- S310G
- Other names
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- Canonical SPDI
- NC_000011.10:108246989:A:G
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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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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00000
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00002
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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ATM | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
10833 | 17429 |
Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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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Likely benign (2) |
criteria provided, single submitter
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Jan 5, 2024 | RCV000167964.10 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jan 4, 2024 | RCV000219840.10 | |
Uncertain significance (2) |
criteria provided, single submitter
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Jul 17, 2022 | RCV000481289.5 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Mar 3, 2024 | RCV003338436.4 |
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
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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
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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
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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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Uncertain significance
(Jul 17, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV000569907.6
First in ClinVar: Apr 29, 2017 Last updated: Mar 04, 2023 |
Comment:
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not … (more)
Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge (less)
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Uncertain significance
(Jan 04, 2024)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000687882.5
First in ClinVar: Feb 19, 2018 Last updated: Feb 14, 2024 |
Comment:
This missense variant replaces serine with glycine at codon 310 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure … (more)
This missense variant replaces serine with glycine at codon 310 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. In a large international case-control meta-analysis, this variant was reported in 1/60465 breast cancer cases and 1/53460 controls (PMID: 33471991). This variant has been identified in 4/250870 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less)
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Likely benign
(Jan 05, 2024)
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criteria provided, single submitter
Method: clinical testing
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Ataxia-telangiectasia syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000218612.10
First in ClinVar: Mar 29, 2015 Last updated: Feb 28, 2024 |
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Uncertain significance
(Oct 03, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000273551.7
First in ClinVar: May 29, 2016 Last updated: May 01, 2024 |
Comment:
The p.S310G variant (also known as c.928A>G), located in coding exon 7 of the ATM gene, results from an A to G substitution at nucleotide … (more)
The p.S310G variant (also known as c.928A>G), located in coding exon 7 of the ATM gene, results from an A to G substitution at nucleotide position 928. The serine at codon 310 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. (less)
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004047091.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The missense variant c.928A>G (p.Ser310Gly) in ATM gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. … (more)
The missense variant c.928A>G (p.Ser310Gly) in ATM gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant has been reported to the ClinVar database as Uncertain Significance. The p.Ser310Gly variant is novel (not in any individuals) in 1000 Genomes. The amino acid Ser at position 310 is changed to a Gly changing protein sequence and it might alter its composition and physico-chemical properties. The residue is conserved across species. The amino acid change p.Ser310Gly in ATM is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significant. (less)
Clinical Features:
Neoplasm (present)
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Uncertain significance
(Mar 03, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial cancer of breast
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV005056923.1
First in ClinVar: Jun 17, 2024 Last updated: Jun 17, 2024 |
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Uncertain significance
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
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Ataxia-telangiectasia
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001456871.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001549215.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The ATM p.Ser310Gly variant was not identified in the literature nor was it identified in the COGR, Cosmic, MutDB, or LOVD 3.0 databases. The variant … (more)
The ATM p.Ser310Gly variant was not identified in the literature nor was it identified in the COGR, Cosmic, MutDB, or LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs745773225) as “With Uncertain significance allele”, and in ClinVar (4x as uncertain significance by Invitae, Ambry Genetics, GeneDx, Color Genomics). The variant was identified in control databases in 4 of 245900 chromosomes at a frequency of 0.000016 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the South Asian population in 4 of 30778 chromosomes (freq: 0.00013). It was not observed in the African, “Other”, Latino, European Non-Finnish, Ashkenazi Jewish, East Asian, or Finnish populations. The p.Ser310 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 2 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. (less)
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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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Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women. | Breast Cancer Association Consortium | The New England journal of medicine | 2021 | PMID: 33471991 |
Text-mined citations for rs745773225 ...
HelpRecord last updated Sep 29, 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.