NM_001201543.2(FAM161A):c.1309A>T (p.Arg437Ter) AND Retinitis pigmentosa

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Apr 1, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000778621.11

Allele description [Variation Report for NM_001201543.2(FAM161A):c.1309A>T (p.Arg437Ter)]

NM_001201543.2(FAM161A):c.1309A>T (p.Arg437Ter)

Gene:

FAM161A:FAM161 centrosomal protein A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2p15

Genomic location:

Preferred name:

NM_001201543.2(FAM161A):c.1309A>T (p.Arg437Ter)

HGVS:

NC_000002.12:g.61839695T>A
NG_028125.1:g.19449A>T
NM_001201543.2:c.1309A>TMANE SELECT
NM_032180.3:c.1309A>T
NP_001188472.1:p.Arg437Ter
NP_115556.2:p.Arg437Ter
NC_000002.11:g.62066830T>A
NM_001201543.1:c.1309A>T
NM_032180.2:c.1309A>T
NP_115556.2:p.Arg437*
NR_037710.2:n.1272A>T

Protein change:

R437*; ARG437TER

Links:

OMIM: 613596.0002; dbSNP: rs200691042

NCBI 1000 Genomes Browser:

rs200691042

Molecular consequence:

NR_037710.2:n.1272A>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001201543.2:c.1309A>T - nonsense - [Sequence Ontology: SO:0001587]
NM_032180.3:c.1309A>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Retinitis pigmentosa (RP)
Synonyms:: Tapetoretinal degeneration
Identifiers:: MONDO: MONDO:0019200; MeSH: D012174; MedGen: C0035334; Orphanet: 791; OMIM: 268000; OMIM: PS268000

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c1galt1c1 [Callorhinchus milii]
c1galt1c1 [Callorhinchus milii]
Gene ID:103178564

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000914934	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (Sep 19, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25999674, 26113502, 25097241, 20705278, 26574802 Citation Link,
SCV000926588	Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet - VeluxRD	no assertion criteria provided	Pathogenic (Apr 1, 2018)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV001452512	Natera, Inc.	no assertion criteria provided	Pathogenic (Sep 16, 2020)	germline	clinical testing
SCV001950276	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 1, 2021)	germline	curation	PubMed (9) [See all records that cite these PMIDs] 30718709, 26574802, 26113502, 25999674, 25525159, 25097241, 20705278, 25741868, 34906470

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	curation
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Molecular genetic analysis using targeted NGS analysis of 677 individuals with retinal dystrophy.

Jespersgaard C, Fang M, Bertelsen M, Dang X, Jensen H, Chen Y, Bech N, Dai L, Rosenberg T, Zhang J, Møller LB, Tümer Z, Brøndum-Nielsen K, Grønskov K.

Sci Rep. 2019 Feb 4;9(1):1219. doi: 10.1038/s41598-018-38007-2.

PubMed [citation]

PMID:: 30718709
PMCID:: PMC6362094

A Nonsense Mutation in FAM161A Is a Recurrent Founder Allele in Dutch and Belgian Individuals With Autosomal Recessive Retinitis Pigmentosa.

Van Schil K, Klevering BJ, Leroy BP, Pott JW, Bandah-Rozenfeld D, Zonneveld-Vrieling MN, Sharon D, den Hollander AI, Cremers FP, De Baere E, Collin RW, van den Born LI.

Invest Ophthalmol Vis Sci. 2015 Nov;56(12):7418-26. doi: 10.1167/iovs.15-17920.

PubMed [citation]

PMID:: 26574802

See all PubMed Citations (9)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000914934.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The FAM161A c.1309A>T (p.Arg437Ter) variant has been reported in at least five studies in 18 individuals with autosomal recessive retinitis pigmentosa, including 12 in a homozygous state, five in a compound heterozygous state, and one in a heterozygous state in whom a second variant was not identified (Langmann et al. 2010; Wang et al. 2014; Rose et al. 2015; Van Schil et al. 2015; van Huet et al. 2015). These patients were unrelated, except for two sets of siblings who were homozygous for the p.Arg437Ter variant (Van Schil et al. 2015; Rose et al. 2015). The p.Arg437Ter variant was absent from 400 control chromosomes and is reported at a frequency of 0.00061 in the European American population of the Exome Sequencing Project. Based on the collective evidence, the p.Arg437Ter variant is classified as pathogenic for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet - VeluxRD, SCV000926588.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Natera, Inc., SCV001452512.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001950276.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (9)

Description

The p.Arg437Ter variant in FAM161A was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PVS1, PM2, PM3. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 10, 2024

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