ClinVar Genomic variation as it relates to human health
NM_001201543.2(FAM161A):c.1153C>G (p.Gln385Glu)
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(1); Benign(1); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001201543.2(FAM161A):c.1153C>G (p.Gln385Glu)
Variation ID: 96216 Accession: VCV000096216.24
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2p15 2: 61839851 (GRCh38) [ NCBI UCSC ] 2: 62066986 (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 Dec 15, 2018 Apr 15, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001201543.2:c.1153C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001188472.1:p.Gln385Glu missense NM_032180.3:c.1153C>G NP_115556.2:p.Gln385Glu missense NR_037710.2:n.1116C>G non-coding transcript variant NC_000002.12:g.61839851G>C NC_000002.11:g.62066986G>C NG_028125.1:g.19293C>G - Protein change
- Q385E
- Other names
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- Canonical SPDI
- NC_000002.12:61839850:G:C
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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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0.00080 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00062
1000 Genomes Project 0.00080
Trans-Omics for Precision Medicine (TOPMed) 0.00278
The Genome Aggregation Database (gnomAD) 0.00309
The Genome Aggregation Database (gnomAD), exomes 0.00333
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00352
Exome Aggregation Consortium (ExAC) 0.00376
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
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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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FAM161A | - | - |
GRCh38 GRCh37 |
760 | 850 |
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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Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Jan 31, 2024 | RCV000416124.28 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001138007.12 | |
Likely benign (1) |
no assertion criteria provided
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Jun 17, 2020 | RCV001274720.9 | |
Likely benign (1) |
criteria provided, single submitter
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Sep 13, 2019 | RCV003952528.1 |
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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Uncertain significance
(Aug 16, 2013)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000114246.8
First in ClinVar: Jan 17, 2014 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 3
Sex: mixed
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Likely benign
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Retinitis pigmentosa
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001298015.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
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Benign
(Jan 31, 2024)
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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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Invitae
Accession: SCV001109025.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
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Likely benign
(Sep 13, 2019)
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criteria provided, single submitter
Method: clinical testing
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FAM161A-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004771653.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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Likely benign
(Aug 01, 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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV000493669.9
First in ClinVar: Jan 30, 2017 Last updated: Apr 15, 2024 |
Comment:
FAM161A: BP4, BS1
Number of individuals with the variant: 1
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Likely benign
(Jun 17, 2020)
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no assertion criteria provided
Method: clinical testing
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Retinitis pigmentosa type 28
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV001459100.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Likely benign
(-)
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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: SCV001551851.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
The FAM161A p.Gln385Glu variant was identified in 1/273 unrelated patients with retinitis pigmentosa (freq=0.002) and 2/270 healthy controls (freq=0.004) (Venturini_2014_PMID: 24651477). There are also no … (more)
The FAM161A p.Gln385Glu variant was identified in 1/273 unrelated patients with retinitis pigmentosa (freq=0.002) and 2/270 healthy controls (freq=0.004) (Venturini_2014_PMID: 24651477). There are also no pathogenic missense variants in FAM161A reported in ClinVar. The variant was also identified in dbSNP (ID: rs139266382), LOVD 3.0 (reported as likely benign) and ClinVar (classified as a variant of uncertain significance by EGL Genetic Diagnostics and Praxis fuer Humangenetik Tuebingen). The variant was not identified in Cosmic. The variant was identified in control databases in 945 of 279988 chromosomes (5 homozygous) at a frequency of 0.003375 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 785 of 127800 chromosomes (freq: 0.006142), Other in 17 of 7126 chromosomes (freq: 0.002386), European (Finnish) in 59 of 25038 chromosomes (freq: 0.002356), African in 26 of 24182 chromosomes (freq: 0.001075), South Asian in 25 of 30600 chromosomes (freq: 0.000817), Latino in 28 of 35366 chromosomes (freq: 0.000792) and Ashkenazi Jewish in 5 of 10342 chromosomes (freq: 0.000484); it was not observed in the East Asian population. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, and GeneSplicer) do not predict a difference in splicing. The p.Gln385 residue is not conserved in mammals and four out of five computational analyses (SIFT, AlignGVGD, BLOSUM, and MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. (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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Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa. | Venturini G | PloS one | 2014 | PMID: 24651477 |
Nonsense mutations in FAM161A cause RP28-associated recessive retinitis pigmentosa. | Langmann T | American journal of human genetics | 2010 | PMID: 20705278 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=FAM161A | - | - | - | - |
Text-mined citations for rs139266382 ...
HelpRecord last updated May 01, 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.