Submissions for variant NM_000153.4(GALC):c.658C>T (p.Arg220Ter)

dbSNP: rs766310671

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169413	SCV000220818	likely pathogenic	Galactosylceramide beta-galactosidase deficiency	2014-10-20	criteria provided, single submitter	literature only
Eurofins Ntd Llc (ga)	RCV000727578	SCV000854820	pathogenic	not provided	2017-08-31	criteria provided, single submitter	clinical testing
Invitae	RCV000169413	SCV000939629	pathogenic	Galactosylceramide beta-galactosidase deficiency	2024-01-31	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg220*) in the GALC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALC are known to be pathogenic (PMID: 7437911, 9272171, 16607461). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individuals with Krabbe disease (PMID: 16607461, 24252386). This variant is also known as R204X. ClinVar contains an entry for this variant (Variation ID: 189024). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Laboratoire de Génétique Moléculaire, CHU Bordeaux	RCV000727578	SCV001468955	pathogenic	not provided		criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000727578	SCV002021222	pathogenic	not provided	2021-08-12	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000169413	SCV001454071	pathogenic	Galactosylceramide beta-galactosidase deficiency	2020-09-16	no assertion criteria provided	clinical testing