Submissions for variant NM_003098.3(SNTA1):c.701+10G>A

gnomAD frequency: 0.00419  dbSNP: rs6057846

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000529919	SCV000627703	benign	Long QT syndrome	2024-01-20	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000781873	SCV000920252	benign	not specified	2018-09-17	criteria provided, single submitter	clinical testing	Variant summary: SNTA1 c.701+10G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0012 in 277038 control chromosomes, predominantly within the African subpopulation, at a frequency of 0.013, in the gnomAD database, including 4 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 1300 fold of the estimated maximal expected allele frequency for a pathogenic variant in SNTA1 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.701+10G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001712488	SCV001943948	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002506296	SCV002807283	benign	Long QT syndrome 12	2021-09-29	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000781873	SCV001926181	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000781873	SCV001928213	benign	not specified		no assertion criteria provided	clinical testing