ClinVar

Description

The MSH6 c.-4C>T variant was not identified in the literature nor was it identified in the UMD-LSDB database. The variant was identified in dbSNP (rs1114167784) as “with likely benign, uncertain significance allele” and ClinVar (classified as likely benign by Color). The variant was identified in control databases in 1 of 243,944 chromosomes at a frequency of 0.000004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 1 of 109,480 chromosomes (freq: 0.000009), while the variant was not observed in the African, Latino, Ashkenazi Jewish, East Asian, Finnish, Other and South Asian populations. The variant lies 4 base pairs upstream of the ATG start site and is part of the Kozak consensus sequence, which is important for translation initiation; although a C is generally present at the -4 position, it is known to vary at this position. The variant occurs at a non-highly conserved nucleotide outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predicted a greater than 10% difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.