Submissions for variant NM_182961.4(SYNE1):c.19534G>T (p.Ala6512Ser)

gnomAD frequency: 0.00010  dbSNP: rs149272010

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000335180	SCV000338826	benign	not specified	2018-07-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000283633	SCV000461045	uncertain significance	Autosomal recessive ataxia, Beauce type	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000320028	SCV000461046	benign	Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000335180	SCV000621145	uncertain significance	not specified	2017-09-26	criteria provided, single submitter	clinical testing	The A6441S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A6441S variant is observed in 155/10,150 (1.53%) alleles from individuals of Ashkenazi Jewish background in large population cohorts, which is greater than expected for this disorder (Lek et al., 2016). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000551091	SCV000649086	benign	Autosomal recessive ataxia, Beauce type; Emery-Dreifuss muscular dystrophy 4, autosomal dominant	2024-01-10	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000335180	SCV001880840	benign	not specified	2021-03-31	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003430819	SCV004160527	benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	SYNE1: BP4, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV004535354	SCV004727325	benign	SYNE1-related disorder	2019-08-01	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).