This sequence change creates a premature translational stop signal (p.Cys501Valfs*4) in the FAM161A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAM161A are known to be pathogenic (PMID: 20705278, 20705279, 24651477). This variant is present in population databases (rs767414973, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with retinitis pigmentosa or a retinal dystrophy (PMID: 23591405, 25097241, 26574802). ClinVar contains an entry for this variant (Variation ID: 552429). For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_001201543.2(FAM161A):c.1501del (p.Cys501fs)
Germline
Classification
Help
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.
(14)
Help
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.
Pathogenic/Likely pathogenic
14
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_001201543.2(FAM161A):c.1501del (p.Cys501fs)
Variation ID: 552429 Accession: VCV000552429.48
- Type and length
-
Deletion, 1 bp
- Location
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Cytogenetic: 2p15 2: 61839503 (GRCh38) [ NCBI UCSC ] 2: 62066638 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Aug 5, 2018 Oct 20, 2024 Mar 28, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001201543.2:c.1501del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001188472.1:p.Cys501fs frameshift NM_032180.3:c.1501del NP_115556.2:p.Cys501fs frameshift NR_037710.2:n.1464del non-coding transcript variant NC_000002.12:g.61839503del NC_000002.11:g.62066638del NG_028125.1:g.19641del - Protein change
- C501fs
- Other names
- -
- Canonical SPDI
- NC_000002.12:61839502:A:
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Exome Aggregation Consortium (ExAC) 0.00003
The Genome Aggregation Database (gnomAD) 0.00004
Trans-Omics for Precision Medicine (TOPMed) 0.00005
The Genome Aggregation Database (gnomAD), exomes 0.00006
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| FAM161A | - | - |
GRCh38 GRCh37 |
781 | 874 | |
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (5) |
criteria provided, multiple submitters, no conflicts
|
Mar 28, 2024 | RCV000667686.15 | |
| Likely pathogenic (1) |
no assertion criteria provided
|
Apr 1, 2018 | RCV000787605.2 | |
| Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Dec 26, 2023 | RCV000733055.37 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jun 16, 2019 | RCV001073558.4 | |
|
FAM161A-related disorder
|
Pathogenic (1) |
no assertion criteria provided
|
May 29, 2024 | RCV004758047.1 |
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. |
|
|---|---|---|---|---|---|
|
Pathogenic
(Jun 19, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 28
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000792174.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
|
|
|
Pathogenic
(Apr 25, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000861074.1
First in ClinVar: Dec 16, 2018 Last updated: Dec 16, 2018 |
Number of individuals with the variant: 1
Sex: mixed
|
|
|
Pathogenic
(Jun 16, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Retinal dystrophy
Affected status: yes
Allele origin:
germline
|
Blueprint Genetics
Accession: SCV001239109.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020
Comment:
My Retina Tracker patient
|
|
|
|
Likely pathogenic
(Mar 30, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 28
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003831198.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Dec 26, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001228083.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Cys501Valfs*4) in the FAM161A gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Cys501Valfs*4) in the FAM161A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAM161A are known to be pathogenic (PMID: 20705278, 20705279, 24651477). This variant is present in population databases (rs767414973, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with retinitis pigmentosa or a retinal dystrophy (PMID: 23591405, 25097241, 26574802). ClinVar contains an entry for this variant (Variation ID: 552429). For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Mar 28, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Retinitis pigmentosa 28
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004195943.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(May 01, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV001246770.26
First in ClinVar: May 12, 2020 Last updated: Oct 20, 2024 |
Number of individuals with the variant: 1
|
|
|
Pathogenic
(Sep 01, 2016)
|
no assertion criteria provided
Method: clinical testing
|
Retinitis pigmentosa 28
Affected status: yes
Allele origin:
inherited
|
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Accession: SCV000804652.2
First in ClinVar: Sep 10, 2018 Last updated: Sep 10, 2018 |
Number of individuals with the variant: 1
|
|
|
Likely pathogenic
(Apr 01, 2018)
|
no assertion criteria provided
Method: research
|
Retinitis pigmentosa
Affected status: yes
Allele origin:
unknown
|
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet
Study: VeluxRD
Accession: SCV000926589.2 First in ClinVar: Jul 21, 2019 Last updated: Sep 03, 2023 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001920389.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
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: SCV001955058.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
|
|
|
Pathogenic
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001980026.1 First in ClinVar: Oct 16, 2021 Last updated: Oct 16, 2021 |
|
|
|
Pathogenic
(Aug 03, 2020)
|
no assertion criteria provided
Method: clinical testing
|
Retinitis pigmentosa type 28
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002076601.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
|
|
Pathogenic
(May 29, 2024)
|
no assertion criteria provided
Method: clinical testing
|
FAM161A-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV005365912.1
First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024 |
Comment:
The FAM161A c.1501delT variant is predicted to result in a frameshift and premature protein termination (p.Cys501Valfs*4). This variant has been reported in the homozygous and … (more)
The FAM161A c.1501delT variant is predicted to result in a frameshift and premature protein termination (p.Cys501Valfs*4). This variant has been reported in the homozygous and compound heterozygous state in individuals with retinitis pigmentosa (Table S1, Glöckle et al 2014. PubMed ID: 23591405; Wang et al. 2014. PubMed ID: 25097241; Table S1, Weisschuh et al. 2020. PubMed ID: 32531858). This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in FAM161A are expected to be pathogenic, and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/552429). Given the evidence, we interpret this variant as pathogenic. (less)
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Comment:
Comment:
The FAM161A c.1501delT variant is predicted to result in a frameshift and premature protein termination (p.Cys501Valfs*4). This variant has been reported in the homozygous and compound heterozygous state in individuals with retinitis pigmentosa (Table S1, Glöckle et al 2014. PubMed ID: 23591405; Wang et al. 2014. PubMed ID: 25097241; Table S1, Weisschuh et al. 2020. PubMed ID: 32531858). This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in FAM161A are expected to be pathogenic, and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/552429). Given the evidence, we interpret this variant as pathogenic.
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. |
Comment:
This sequence change creates a premature translational stop signal (p.Cys501Valfs*4) in the FAM161A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FAM161A are known to be pathogenic (PMID: 20705278, 20705279, 24651477). This variant is present in population databases (rs767414973, gnomAD 0.02%). This premature translational stop signal has been observed in individuals with retinitis pigmentosa or a retinal dystrophy (PMID: 23591405, 25097241, 26574802). ClinVar contains an entry for this variant (Variation ID: 552429). For these reasons, this variant has been classified as Pathogenic.
Comment:
The FAM161A c.1501delT variant is predicted to result in a frameshift and premature protein termination (p.Cys501Valfs*4). This variant has been reported in the homozygous and compound heterozygous state in individuals with retinitis pigmentosa (Table S1, Glöckle et al 2014. PubMed ID: 23591405; Wang et al. 2014. PubMed ID: 25097241; Table S1, Weisschuh et al. 2020. PubMed ID: 32531858). This variant is reported in 0.013% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in FAM161A are expected to be pathogenic, and this variant has been classified as pathogenic by multiple independent submitters to the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/552429). Given the evidence, we interpret this variant as pathogenic.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy. | Jespersgaard C | Scientific reports | 2019 | PMID: 30718709 |
| A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals With Autosomal Recessive Retinitis Pigmentosa. | Van Schil K | Investigative ophthalmology & visual science | 2015 | PMID: 26574802 |
| Dependable and efficient clinical utility of target capture-based deep sequencing in molecular diagnosis of retinitis pigmentosa. | Wang J | Investigative ophthalmology & visual science | 2014 | PMID: 25097241 |
| Molecular genetics of FAM161A in North American patients with early-onset retinitis pigmentosa. | Venturini G | PloS one | 2014 | PMID: 24651477 |
| Panel-based next generation sequencing as a reliable and efficient technique to detect mutations in unselected patients with retinal dystrophies. | Glöckle N | European journal of human genetics : EJHG | 2014 | PMID: 23591405 |
| Homozygosity mapping reveals null mutations in FAM161A as a cause of autosomal-recessive retinitis pigmentosa. | Bandah-Rozenfeld D | American journal of human genetics | 2010 | PMID: 20705279 |
| 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 rs767414973 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 10, 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.