Submissions for variant NM_000709.4(BCKDHA):c.288C>T (p.His96=)

gnomAD frequency: 0.00043  dbSNP: rs148571328

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723410	SCV000111105	uncertain significance	not provided	2013-09-03	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000270845	SCV000413342	uncertain significance	Maple syrup urine disease	2018-01-12	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.
GeneDx	RCV000723410	SCV000529023	likely benign	not provided	2018-04-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000270845	SCV000835193	uncertain significance	Maple syrup urine disease	2022-10-21	criteria provided, single submitter	clinical testing	This sequence change affects codon 96 of the BCKDHA mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the BCKDHA protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs148571328, gnomAD 0.05%). This variant has been observed in individual(s) with maple syrup urine disease (PMID: 33300147). ClinVar contains an entry for this variant (Variation ID: 93353). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab	RCV000270845	SCV002033684	likely benign	Maple syrup urine disease	2021-11-07	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002514393	SCV003627123	likely benign	Inborn genetic diseases	2022-01-28	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.
Natera, Inc.	RCV001273301	SCV001456197	uncertain significance	Maple syrup urine disease type 1A	2019-11-11	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003964923	SCV004795371	likely benign	BCKDHA-related disorder	2019-04-29	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).