Submissions for variant NM_000153.4(GALC):c.621+5G>A

dbSNP: rs1555383306

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000665486	SCV000789616	likely pathogenic	Galactosylceramide beta-galactosidase deficiency	2017-02-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000665486	SCV004241866	likely pathogenic	Galactosylceramide beta-galactosidase deficiency	2023-12-06	criteria provided, single submitter	clinical testing	Variant summary: GALC c.621+5G>A alters a 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: One predict the variant abolishes a 5' splicing donor site. Two predict the variant weakens a 5' donor site. At least one publication reports experimental evidence that this variant results in skipping of exon 6 (Kukita_1997). The variant was absent in 244428 control chromosomes. c.621+5G>A has been reported in the literature in individuals affected with Krabbe Disease (Kukita_1997). The following publication have been ascertained in the context of this evaluation (PMID: 10464649). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.