rs111033746
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000155.4(GALT):c.634C>T(p.Gln212Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q212Q) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000155.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALT | NM_000155.4 | c.634C>T | p.Gln212Ter | stop_gained | 7/11 | ENST00000378842.8 | |
GALT | NM_001258332.2 | c.307C>T | p.Gln103Ter | stop_gained | 5/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000378842.8 | c.634C>T | p.Gln212Ter | stop_gained | 7/11 | 1 | NM_000155.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251472Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135912
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 727244
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Pathogenic:4
Pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 23, 2022 | Variant summary: GALT c.634C>T (p.Gln212X) 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 4e-06 in 251472 control chromosomes (gnomAD). c.634C>T has been reported in the literature in compound heterozygous state in multiple individuals affected with Galactosemia (e.g. Gathof_1995, Yuzyuk_2018), where the complete lack of enzyme activity was noted in patient derived red blood cells. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2020 | For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with galactosemia (PMID: 8522334). ClinVar contains an entry for this variant (Variation ID: 25234). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln212*) in the GALT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GALT are known to be pathogenic (PMID: 22944367). - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 20, 2024 | - - |
Likely pathogenic, criteria provided, single submitter | literature only | Counsyl | Dec 18, 2014 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 19, 2012 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Mar 14, 2023 | PP4, PM2, PM3, PVS1 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at