Submissions for variant NM_000153.4(GALC):c.1335A>G (p.Leu445=)

gnomAD frequency: 0.00015  dbSNP: rs373277798

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001442743	SCV001645698	likely benign	Galactosylceramide beta-galactosidase deficiency	2023-10-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002271653	SCV002555701	likely benign	not specified	2022-06-07	criteria provided, single submitter	clinical testing	Variant summary: GALC c.1335A>G alters a non-conserved nucleotide resulting in a synonymous change. 4/4 computational tools predict no significant impact on normal splicing, however, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0002 in 248444 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in GALC causing Krabbe Disease (0.0002 vs 0.0022), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1335A>G in individuals affected with Krabbe Disease and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.