ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1468T>A (p.Tyr490Asn) (rs202135871)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498864 SCV000589634 likely pathogenic not provided 2017-06-21 criteria provided, single submitter clinical testing A variant that is likely pathogenic has been identified in the GALC gene. The Y490N variant has been reported previously in an individual with a clinical diagnosis of Krabbe disease who was compound heterozygous for Y490N and a second GALC variant; however, insufficient clinical information was provided to confirm diagnosis (Tappino et al., 2010). In vitro expression studies show that Y490N (referred to as Y474N due to alternative nomenclature) causes a reduction of GALC expression (Saavedra-Matiz et al., 2016). The Y490N variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The Y490N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Counsyl RCV000668258 SCV000792831 uncertain significance Galactosylceramide beta-galactosidase deficiency 2017-07-17 criteria provided, single submitter clinical testing

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.