ClinVar Miner

Submissions for variant NM_000155.4(GALT):c.864C>T (p.Asn288=)

gnomAD frequency: 0.00010  dbSNP: rs372134800
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000508394 SCV000603798 uncertain significance not specified 2017-02-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000545786 SCV000631396 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2024-10-30 criteria provided, single submitter clinical testing This sequence change affects codon 288 of the GALT mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the GALT protein. This variant is present in population databases (rs372134800, gnomAD 0.03%). This variant has been observed in individual(s) with features of galactosemia (PMID: 22944367). ClinVar contains an entry for this variant (Variation ID: 203732). 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 available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl RCV000545786 SCV000791583 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2017-05-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000508394 SCV000919398 uncertain significance not specified 2025-02-27 criteria provided, single submitter clinical testing Variant summary: GALT c.864C>T alters a conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: One predict the variant strengthens a cryptic 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.4e-05 in 251692 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in GALT causing Galactosemia (4.4e-05 vs 0.0029), allowing no conclusion about variant significance. The variant, c.864C>T, has been reported in the literature in two compound heterozygous individuals affected with Galactosemia (McDonald_2009, Boutron_2012). One of these reports also noted that the diagnosis was confirmed by absent GALT activity in erythrocytes in all their cases, though no patient specific data were provided (Boutron 2012). The variant has also been reported in homozygosity in a sample from an individual that had only a residual GALT activity; and although no information was provided on the patient's phenotype, the measured enzyme activity was specific for galactosemia (Yuzyuk_2018). A conference abstract (McDonald 2009) described that cDNA containing the variant of interest (from a proband and probands father) was void of exon 9, although they both had additional variants leading to a complex haplotype (N288N, T292T and H315H) and it is not clear if the exon skipping effect was caused solely by our variant of interest or a combination effect due to this specific haplotype. These data indicate that the variant may be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 22944367, 33636947). ClinVar contains an entry for this variant (Variation ID: 203732). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Mendelics RCV000545786 SCV001137807 uncertain significance Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase 2023-06-02 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV002261002 SCV002540987 uncertain significance not provided 2021-08-30 criteria provided, single submitter clinical testing
Natera, Inc. RCV001271247 SCV001452291 uncertain significance Galactosemia 2020-09-16 no assertion criteria provided clinical testing

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