ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.621G>A (p.Lys207=) (rs1428763453)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000664849 SCV000788868 uncertain significance Galactosylceramide beta-galactosidase deficiency 2016-12-23 criteria provided, single submitter clinical testing
Pathology and Clinical Laboratory Medicine,King Fahad Medical City RCV000664849 SCV000996293 pathogenic Galactosylceramide beta-galactosidase deficiency criteria provided, single submitter clinical testing Enzyme deficiency
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001193605 SCV001362550 uncertain significance not specified 2019-03-07 criteria provided, single submitter clinical testing Variant summary: GALC c.621G>A (p.Lys207Lys) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: three predict the variant weakens a 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 243894 control chromosomes (gnomAD). c.621G>A has been reported in the literature in a homozygous individual affected with Krabbe Disease (Wenger_2000), and in a newborn screening sample indicative of low GALC enzyme activity, where the a second mutation was not provided (Orsini_2016). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.