Submissions for variant NM_001110219.3(GJB6):c.476A>G (p.Asn159Ser)

gnomAD frequency: 0.00237  dbSNP: rs35277762

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038707	SCV000062385	benign	not specified	2011-11-07	criteria provided, single submitter	clinical testing	Asn159Ser in exon 3 of GJB6: This variant is not expected to have clinical signi ficance because it has been identified in 0.6% (36/5297) of a broad population ( dbSNP rs35277762).
Eurofins Ntd Llc (ga)	RCV000038707	SCV000331581	likely benign	not specified	2016-06-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000945915	SCV001091989	likely benign	Autosomal recessive nonsyndromic hearing loss 1A; Autosomal recessive nonsyndromic hearing loss 1B; Autosomal dominant nonsyndromic hearing loss 3B; Hidrotic ectodermal dysplasia syndrome	2024-11-25	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001110055	SCV001267441	benign	Hidrotic ectodermal dysplasia syndrome	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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
GeneDx	RCV001762120	SCV001988801	benign	not provided	2021-08-10	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Observed in 205/282878 (0.0725%) alleles in large population cohorts (Lek et al., 2016); In-silico analysis, which includes splice predictors and evolutionary conservation, is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Breakthrough Genomics, Breakthrough Genomics	RCV001762120	SCV005219308	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004541116	SCV004780555	benign	GJB6-related disorder	2019-11-06	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).