rs111033831
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM2PM5PP3_StrongPP5
The NM_000155.4(GALT):c.815G>A(p.Arg272His) variant causes a missense change. The variant allele was found at a frequency of 0.00000684 in 1,461,024 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R272G) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000155.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GALT | NM_000155.4 | c.815G>A | p.Arg272His | missense_variant | 8/11 | ENST00000378842.8 | NP_000146.2 | |
GALT | NM_001258332.2 | c.488G>A | p.Arg163His | missense_variant | 6/9 | NP_001245261.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000378842.8 | c.815G>A | p.Arg272His | missense_variant | 8/11 | 1 | NM_000155.4 | ENSP00000368119 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000797 AC: 2AN: 250824Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135664
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461024Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 726886
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Pathogenic:4
Likely pathogenic, criteria provided, single submitter | clinical testing | Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India | - | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 19, 2023 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 272 of the GALT protein (p.Arg272His). This variant is present in population databases (rs111033831, gnomAD 0.003%). This missense change has been observed in individual(s) with galactosemia (PMID: 22944367; Invitae). ClinVar contains an entry for this variant (Variation ID: 38277). 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. This variant disrupts the p.Arg272 amino acid residue in GALT. Other variant(s) that disrupt this residue have been observed in individuals with GALT-related conditions (PMID: 20151200), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Apr 12, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 20, 2023 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 06, 2017 | Variant summary: The GALT c.815G>A (p.Arg272His) variant involves the alteration of a conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 2/245620 control chromosomes (gnomAD) at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic GALT variant (0.0028868). This variant has been reported in three patients in compound heterozygous state with another pathogenic mutation (Boutron_2012). Another missense change at the same residue Arg272Gly has also been reported in a patient with galactesemia and is classified as pathogenic by a database in ClinVar. Taken together, this variant is classified as VUS - possibly pathogenic. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 26, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at