ClinVar Miner

Submissions for variant NM_006922.4(SCN3A):c.5407G>A (p.Asp1803Asn)

gnomAD frequency: 0.00040  dbSNP: rs3731762
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Epilepsy Sodium Channel Variant Curation Expert Panel, Clingen RCV004577518 SCV005061727 benign Early infantile epileptic encephalopathy with suppression bursts 2024-05-09 reviewed by expert panel curation The c.5407G>A variant in SCN3A is a missense variant predicted to cause substitution of Aspartic acid by Asparagine at amino acid 1803 (p.Asp1803Asn). The highest population minor allele frequency in gnomAD v2.1.1 is 0.01653 (143/8652 alleles) in East Asian population, which is higher than the ClinGen Epilepsy Sodium Channel threshold (0.0001) for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.114, which is below the threshold of 0.183, evidence that does not predict a damaging effect on SCN3A function (BP4_moderate). This variant resides within a region of SCN3A that is defined as a mutational hotspot by the ClinGen sodium channel VCEP (PM1). Although there are both pathogenic and benign types of evidence for this variant, the high frequency of this variant in gnomAD strongly supports a benign classification, and the only evidence in support of pathogenicity is based on a prediction that this variant may lie in a mutational hotspot. In summary, this variant meets the criteria to be classified as Benign for autosomal dominant developmental and epileptic encephalopathy based on ACMG/AMP criteria applied, as specified by the ClinGen Epilepsy Sodium Channel VCEP: BA1, BP4, and PM1. (VCEP specifications version 1; 6/27/2023).
Labcorp Genetics (formerly Invitae), Labcorp RCV000227630 SCV000289607 benign not provided 2024-01-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004541440 SCV004798001 benign SCN3A-related disorder 2024-02-27 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).

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.