ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.673G>A (p.Ala225Thr)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Molecular and Human Genetics, Baylor College of Medicine RCV001195147 SCV001334106 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2020-04-16 criteria provided, single submitter clinical testing
Invitae RCV001195147 SCV001517585 uncertain significance Galactosylceramide beta-galactosidase deficiency 2020-08-30 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 225 of the GALC protein (p.Ala225Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with Krabbe disease (PMID: 27638593, 26795590). ClinVar contains an entry for this variant (Variation ID: 915993). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALC protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV001195147 SCV001528220 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2018-02-01 criteria provided, single submitter clinical testing This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. The GALC c.673G>A (p.A225T) variant has been previously reported in three infants who were suspected of GALC deficiency from new born screening; in vitro functional studies showed that the mutant enzyme presented with decreased activity [PMID 26795590, 27638593]
Mayo Clinic Laboratories, Mayo Clinic RCV001508371 SCV001714489 likely pathogenic not provided 2019-11-03 criteria provided, single submitter clinical testing PS3, PM2, PM5

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.