Submissions for variant NM_001201543.2(FAM161A):c.1133T>G (p.Leu378Arg)

gnomAD frequency: 0.00389  dbSNP: rs187695569

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153227	SCV000202701	uncertain significance	not provided	2015-11-07	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000765693	SCV000897035	uncertain significance	Retinitis pigmentosa 28	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000153227	SCV001110408	benign	not provided	2025-01-21	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000153227	SCV001152317	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	FAM161A: BP4, BS2
Illumina Laboratory Services, Illumina	RCV001138008	SCV001298016	uncertain significance	Retinitis pigmentosa	2017-04-27	criteria provided, single submitter	clinical testing	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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001844052	SCV002103609	benign	not specified	2022-02-18	criteria provided, single submitter	clinical testing	Variant summary: FAM161A c.1133T>G (p.Leu378Arg) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.003 in 248790 control chromosomes, predominantly within the Non-Finnish European subpopulation in the gnomAD database at a frequency of 0.0042, including 3 homozygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database (v2.1 dataset) is approximately 6.7-fold of the estimated maximal expected allele frequency for a pathogenic variant in FAM161A causing Retinitis Pigmentosa phenotype (0.00063). The variant was also observed in the Amish subpopulation in 66/910 alleles, including 7 homozygotes, with an allele frequency of 0.0725 in the gnomAD v3.1 dataset. These data strongly suggest that the variant is a benign polymorphism. Six submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 without evidence for independent evaluation, and classified the variant as VUS (n=3), likely benign (n=2) / benign (n=1). Based on the evidence outlined above, the variant was classified as benign.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000765693	SCV006056302	likely benign	Retinitis pigmentosa 28	2021-08-12	criteria provided, single submitter	research
Natera, Inc.	RCV000765693	SCV001459101	likely benign	Retinitis pigmentosa 28	2020-06-11	no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000153227	SCV001799687	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000153227	SCV001917773	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000153227	SCV001966165	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003907444	SCV004724767	likely benign	FAM161A-related disorder	2020-02-19	no assertion criteria provided	clinical testing	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).