ClinVar

Description

Variant summary: GALK1 c.1031C>T (p.Thr344Met) results in a non-conservative amino acid change located in the GHMP kinase, C-terminal domain (IPR013750) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.5e-05 in 205992 control chromosomes. c.1031C>T has been reported in the literature in at-least three Japanese individuals affected with Deficiency Of Galactokinase (example, Asada_1999). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal GALK enzyme activity in patient erythrocytes as well as in an in-vitro COS cell expression system. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.