Submissions for variant NM_001372044.2(SHANK3):c.3257G>T (p.Gly1086Val)

gnomAD frequency: 0.00061  dbSNP: rs767058690

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002312289	SCV000846122	likely benign	Inborn genetic diseases	2018-12-07	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
GeneDx	RCV001613438	SCV001838913	benign	not provided	2020-03-02	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 25188300, 20385823, 28371232)
CeGaT Center for Human Genetics Tuebingen	RCV001613438	SCV004155326	likely benign	not provided	2024-06-01	criteria provided, single submitter	clinical testing	SHANK3: BS1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479205	SCV004223652	uncertain significance	not specified	2023-11-10	criteria provided, single submitter	clinical testing	Variant summary: SHANK3 c.3257G>T (p.Arg1086Leu) results in a non-conservative amino acid change in the encoded protein sequence. Two of two in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 127098 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3257G>T in individuals affected with Phelan-McDermid Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV004544965	SCV004789611	likely benign	SHANK3-related disorder	2022-05-22	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).