chr10-124403892-G-A
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_000274.4(OAT):c.677C>T(p.Ala226Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,936 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 (★★). Synonymous variant affecting the same amino acid position (i.e. A226A) has been classified as Likely benign.
Frequency
Consequence
NM_000274.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OAT | NM_000274.4 | c.677C>T | p.Ala226Val | missense_variant | 6/10 | ENST00000368845.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OAT | ENST00000368845.6 | c.677C>T | p.Ala226Val | missense_variant | 6/10 | 1 | NM_000274.4 | P1 | |
OAT | ENST00000539214.5 | c.263C>T | p.Ala88Val | missense_variant | 5/9 | 1 | |||
OAT | ENST00000467675.5 | n.478C>T | non_coding_transcript_exon_variant | 5/7 | 5 | ||||
OAT | ENST00000483711.1 | n.523C>T | non_coding_transcript_exon_variant | 2/2 | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251464Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461782Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727214
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74324
ClinVar
Submissions by phenotype
Ornithine aminotransferase deficiency Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 226 of the OAT protein (p.Ala226Val). This variant is present in population databases (rs121965059, gnomAD 0.004%). This missense change has been observed in individual(s) with gyrate atrophy (PMID: 1427882, 7887415). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 181). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on OAT protein function. Experimental studies have shown that this missense change affects OAT function (PMID: 7887415, 23076989). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 07, 2023 | - - |
Gyrate atrophy of choroid and retina with pyridoxine-responsive ornithinemia Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Mar 01, 1995 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at