Submissions for variant NM_000155.4(GALT):c.1055A>G (p.Glu352Gly)

dbSNP: rs1821203474

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001201298	SCV001372433	uncertain significance	not specified	2025-01-07	criteria provided, single submitter	clinical testing	Variant summary: GALT c.1055A>G (p.Glu352Gly) results in a non-conservative amino acid change located in the Galactose-1-phosphate uridyl transferase, C-terminal domain (IPR005850) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251424 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1055A>G has been reported in the literature in an individual with a positive newborn screening result for GALT-related disease (Labcorp (formerly Invitae)). 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. ClinVar contains an entry for this variant (Variation ID: 933208). Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001360296	SCV001556209	likely pathogenic	Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase	2023-04-24	criteria provided, single submitter	clinical testing	This variant disrupts the p.Glu352 amino acid residue in GALT. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 34030713). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 352 of the GALT protein (p.Glu352Gly). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with a positive newborn screening result for GALT-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 933208). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt GALT protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Natera, Inc.	RCV001828616	SCV002085258	uncertain significance	Galactosemia	2019-12-31	no assertion criteria provided	clinical testing