Submissions for variant NM_000155.4(GALT):c.1052del (p.Pro351fs)

dbSNP: rs111033813

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723535	SCV000224783	pathogenic	not provided	2015-05-28	criteria provided, single submitter	clinical testing
Counsyl	RCV000173648	SCV000485509	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2015-12-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000173648	SCV000919403	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2018-08-27	criteria provided, single submitter	clinical testing	Variant summary: GALT c.1052delC (p.Pro351LeufsX8) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4.1e-06 in 246230 control chromosomes (gnomAD). The variant, c.1052delC, has been reported in the literature in individuals affected with Galactosemia. These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Invitae	RCV000173648	SCV002256413	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2024-01-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Pro351Leufs*8) in the GALT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 29 amino acid(s) of the GALT protein. This variant is present in population databases (rs749823588, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with GALT-related conditions. ClinVar contains an entry for this variant (Variation ID: 193559). This variant disrupts a region of the GALT protein in which other variant(s) (p.Glu363Lys) have been determined to be pathogenic (PMID: 21150919, 30718057). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000173648	SCV004198518	pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2023-08-10	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001831994	SCV002085256	likely pathogenic	Galactosemia	2020-07-29	no assertion criteria provided	clinical testing