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

gnomAD frequency: 0.00030  dbSNP: rs200691042

Total submissions: 24

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153226	SCV000229237	pathogenic	not provided	2016-08-15	criteria provided, single submitter	clinical testing
GeneDx	RCV000153226	SCV000329583	pathogenic	not provided	2022-02-09	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 30718709, 25097241, 25525159, 20705278, 28559085, 26113502, 26574802, 25999674, 31589614, 34426522, 33576794)
Counsyl	RCV000000053	SCV000487029	pathogenic	Retinitis pigmentosa 28	2016-10-18	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000000053	SCV000894286	pathogenic	Retinitis pigmentosa 28	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000778621	SCV000914934	pathogenic	Retinitis pigmentosa	2017-09-19	criteria provided, single submitter	clinical testing	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000153226	SCV000943915	pathogenic	not provided	2024-11-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg437*) 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 (rs200691042, gnomAD 0.05%). This premature translational stop signal has been observed in individuals with FAM161A-related conditions (PMID: 20705278, 26113502, 26574802). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 36). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics	RCV000787604	SCV001239108	pathogenic	Retinal dystrophy	2019-06-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000153226	SCV001246771	pathogenic	not provided	2023-09-01	criteria provided, single submitter	clinical testing	FAM161A: PM3:Very Strong, PVS1, PM2
Baylor Genetics	RCV000000053	SCV001527850	pathogenic	Retinitis pigmentosa 28	2024-03-25	criteria provided, single submitter	clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear	RCV000000053	SCV001573614	pathogenic	Retinitis pigmentosa 28	2021-04-08	criteria provided, single submitter	research	The FAM161A c.1309A>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. 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.
Genomics England Pilot Project, Genomics England	RCV000000053	SCV001760093	pathogenic	Retinitis pigmentosa 28		criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000153226	SCV001905556	pathogenic	not provided	2021-09-15	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000778621	SCV001950276	pathogenic	Retinitis pigmentosa	2021-04-01	criteria provided, single submitter	curation	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.
Revvity Omics, Revvity	RCV000000053	SCV002022279	pathogenic	Retinitis pigmentosa 28	2020-12-30	criteria provided, single submitter	clinical testing
Genetics and Molecular Pathology, SA Pathology	RCV000000053	SCV002556624	pathogenic	Retinitis pigmentosa 28	2022-01-21	criteria provided, single submitter	clinical testing
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV000787604	SCV005071881	pathogenic	Retinal dystrophy	2023-01-01	criteria provided, single submitter	clinical testing
OMIM	RCV000000053	SCV000020196	pathogenic	Retinitis pigmentosa 28	2010-09-10	no assertion criteria provided	literature only
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000678572	SCV000804651	pathogenic	Cone-rod dystrophy	2016-09-01	no assertion criteria provided	clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000787604	SCV000926587	pathogenic	Retinal dystrophy	2018-04-01	no assertion criteria provided	research
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000778621	SCV000926588	pathogenic	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research
Natera, Inc.	RCV000778621	SCV001452512	pathogenic	Retinitis pigmentosa	2020-09-16	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000153226	SCV001923391	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000153226	SCV001953139	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000153226	SCV001974089	pathogenic	not provided		no assertion criteria provided	clinical testing