rs1131691837
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000155.4(GALT):c.157T>A(p.Trp53Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,850 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 Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_000155.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALT | NM_000155.4 | c.157T>A | p.Trp53Arg | missense_variant | 2/11 | ENST00000378842.8 | |
GALT | NM_001258332.2 | c.-46T>A | 5_prime_UTR_variant | 2/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000378842.8 | c.157T>A | p.Trp53Arg | missense_variant | 2/11 | 1 | NM_000155.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461850Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727226
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2016 | The W53R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The W53R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants in nearby residues (R48C, R51L/Q, G55C) have been reported in the Human Gene Mutation Database in association with galactosemia (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. - |
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 02, 2021 | This sequence change replaces tryptophan with arginine at codon 53 of the GALT protein (p.Trp53Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). 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: 430221). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at