Submissions for variant NM_000520.6(HEXA):c.412+1G>T

dbSNP: rs2140328162

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003502613	SCV004297648	likely pathogenic	Tay-Sachs disease	2024-01-16	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 3 of the HEXA gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with Tay-Sachs disease (PMID: 7837766). ClinVar contains an entry for this variant (Variation ID: 1693585). Studies have shown that disruption of this splice site results in skipping of exon 3 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
MutSpliceDB: a database of splice sites variants effects on splicing, NIH	RCV002261481	SCV002540794	not provided	not provided		no assertion provided	research