Submissions for variant NM_001005273.3(CHD3):c.1235G>A (p.Arg412Gln)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003311322	SCV004007966	likely benign	Inborn genetic diseases	2023-05-31	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.
Pittsburgh Clinical Genomics Laboratory, University of Pittsburgh Medical Center	RCV004784138	SCV005397478	uncertain significance	Snijders Blok-Campeau syndrome	2023-08-01	criteria provided, single submitter	clinical testing	This sequence variant is a single nucleotide substitution (G>A) at position 1412 of the coding sequence of the CHD3 gene that results in an arginine to glutamine amino acid change at residue 471 of the CHD3 protein. This residue falls within the zinc finger domain (Uniprot) which plays an important role in CHD3 function. This variant is absent from ClinVar but is present in 16 of 282576 alleles (0.0057%) in the gnomAD population dataset. Multiple bioinformatic tools predict that this arginine to glutamine amino acid change would be neutral, and the Arg471 residue at this position is highly conserved across the mammalian species examined. Studies examining the functiol consequence of this variant have not been performed, to our knowledge. At this time, there is insufficient evidence to determine if this variant is pathogenic or benign. Therefore, we consider this a variant of uncertain significance. ACMG Criteria: BP4
PreventionGenetics, part of Exact Sciences	RCV003966305	SCV004781607	likely benign	CHD3-related disorder	2023-09-11	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).