ClinVar

Description

Variant summary: CHMP1A c.570-1G>C alters a conserved nucleotide located in a canonical splice-site of the last intron (intron 6) adjacent to the last coding exon 7 of the CHMP1A gene. It is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 3' splice acceptor site while four also predict the variant abolishes a hyopthetical 5' splice donor site of unknown significance. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 193188 control chromosomes. To our knowledge, no occurrence of c.570-1G>C in individuals affected with Pontocerebellar Hypoplasia, Type 8 and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.