ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.1014C>G (p.Gly338=)

gnomAD frequency: 0.00001  dbSNP: rs111033811
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000790690 SCV000331181 likely pathogenic not provided 2015-09-18 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000022262 SCV001576314 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2024-04-20 criteria provided, single submitter clinical testing This sequence change affects codon 338 of the GALT mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GALT protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. This variant is present in population databases (rs111033811, gnomAD 0.003%). This variant has been observed in individual(s) with galactosemia (PMID: 22944367; Invitae). ClinVar contains an entry for this variant (Variation ID: 25316). Studies have shown that this variant results in activation of a new donor splice site in exon 10 and introduces a new termination codon (PMID: 22944367). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000022262 SCV002598562 likely pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-10-27 criteria provided, single submitter clinical testing Variant summary: GALT c.1014C>G alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Three predict the variant creates a cryptic 5' donor site. At least one publication reports experimental evidence that this variant affects mRNA splicing leading to a frameshift with a premature stop codon at nt1027 (p.Tyr339Leufs*5) (example: Boutron_2012). The variant allele was found at a frequency of 1.2e-05 in 251480 control chromosomes (gnomAD). c.1014C>G has been reported in the literature in individuals affected with Galactosemia (examples: Boutron_2012, Lacombe_2015, Yuzyuk_2018 and Jezela-Stanek_2021). The following publications have been ascertained in the context of this evaluation (PMID: 22944367, 34030713, 31194895, 25622686). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV000022262 SCV004198540 pathogenic Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-05-31 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000790690 SCV004226605 pathogenic not provided 2022-09-02 criteria provided, single submitter clinical testing PP4, PM2, PM3_strong, PS3, PS4
Natera, Inc. RCV001835634 SCV002085254 likely pathogenic Galactosemia 2017-03-15 no assertion criteria provided clinical testing

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