ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1731C>T (p.Phe577=) (rs201560122)

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
Illumina Clinical Services Laboratory,Illumina RCV000306103 SCV000389237 likely benign Galactosylceramide beta-galactosidase deficiency 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781393 SCV000919388 benign not specified 2018-11-19 criteria provided, single submitter clinical testing Variant summary: GALC c.1731C>T alters a non-conserved nucleotide resulting in a synonymous change. The variant allele was found at a frequency of 0.0017 in 276260 control chromosomes, predominantly at a frequency of 0.014 within the South Asian subpopulation in the gnomAD database, including 10 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 6-fold of the estimated maximal expected allele frequency for a pathogenic variant in GALC causing Krabbe Disease phenotype (0.0022), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no occurrence of c.1731C>T in individuals affected with Krabbe Disease and no experimental evidence demonstrating its impact on protein function have 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 benign.
Invitae RCV000306103 SCV001013830 benign Galactosylceramide beta-galactosidase deficiency 2020-11-22 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.