rs111033826
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000155.4(GALT):c.553C>T(p.Pro185Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,868 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 Pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P185L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000155.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GALT | NM_000155.4 | c.553C>T | p.Pro185Ser | missense_variant | 6/11 | ENST00000378842.8 | |
GALT | NM_001258332.2 | c.226C>T | p.Pro76Ser | missense_variant | 4/9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GALT | ENST00000378842.8 | c.553C>T | p.Pro185Ser | missense_variant | 6/11 | 1 | NM_000155.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461868Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 727234
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Deficiency of UDPglucose-hexose-1-phosphate uridylyltransferase Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Apr 03, 2021 | For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Pro185 amino acid residue in GALT. Other variant(s) that disrupt this residue have been observed in individuals with GALT-related conditions (PMID: 17876724), which suggests that this may be a clinically significant amino acid residue. This variant has been reported to affect GALT protein function (PMID: 25614870, 25814382). This variant has been observed in individual(s) with galactosemia (PMID: 23749220). ClinVar contains an entry for this variant (Variation ID: 25211). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with serine at codon 185 of the GALT protein (p.Pro185Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at