Submissions for variant NM_182961.4(SYNE1):c.7433C>G (p.Ser2478Cys)

gnomAD frequency: 0.00156  dbSNP: rs149030452

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000263062	SCV000342941	benign	not specified	2016-07-08	criteria provided, single submitter	clinical testing
GeneDx	RCV001705430	SCV000524822	uncertain significance	not provided	2022-07-27	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV000871135	SCV001012741	likely benign	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2024-01-03	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000263062	SCV001477010	benign	not specified	2020-04-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000263062	SCV004121700	likely benign	not specified	2023-10-16	criteria provided, single submitter	clinical testing	Variant summary: SYNE1 c.7454C>G (p.Ser2485Cys) 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 0.00039 in 251270 control chromosomes, predominantly at a frequency of 0.005 within the African or African-American subpopulation in the gnomAD database, strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.7454C>G in individuals affected with Emery-Dreifuss Muscular Dystrophy 4, Autosomal Dominant and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as benign (n=2), likely benign (n=1), or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV003949922	SCV004760053	likely benign	SYNE1-related condition	2022-02-03	criteria provided, single submitter	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).