rs1034294766
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM1PM2PP3_Moderate
The ENST00000357578.8(ALDH5A1):c.250G>A(p.Gly84Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000197 in 1,524,542 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G84R) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000357578.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ALDH5A1 | NM_001080.3 | c.250G>A | p.Gly84Ser | missense_variant | 1/10 | ENST00000357578.8 | NP_001071.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ALDH5A1 | ENST00000357578.8 | c.250G>A | p.Gly84Ser | missense_variant | 1/10 | 1 | NM_001080.3 | ENSP00000350191 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 151992Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000146 AC: 2AN: 1372550Hom.: 0 Cov.: 31 AF XY: 0.00000148 AC XY: 1AN XY: 677012
GnomAD4 genome AF: 0.00000658 AC: 1AN: 151992Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74250
ClinVar
Submissions by phenotype
Succinate-semialdehyde dehydrogenase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 09, 2022 | This variant is not present in population databases (gnomAD no frequency). 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. 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 ALDH5A1 protein function. ClinVar contains an entry for this variant (Variation ID: 1422649). This variant has not been reported in the literature in individuals affected with ALDH5A1-related conditions. This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 84 of the ALDH5A1 protein (p.Gly84Ser). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at