ClinVar

Description

Variant summary: GALT c.640G>A (p.Gly214Arg) results in a non-conservative amino acid change located in the C-terminal domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 30936 control chromosomes (in gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, p.Gly214Arg, has been reported in the literature to be detected in a laboratory sample with severely decreased GALT enzyme activity, however no phenotype information was provided. In addition, authors noted that further investigations would be necessary rule out analytical artifacts (Yuzyuk_2018), thus this report does not provide unequivocal conclusions about association of the variant with Galactosemia. To our knowledge, no experimental evidence demonstrating an impact on protein function has 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 uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.