rs121965048
Variant summary
Our verdict is Likely pathogenic. Variant got 9 ACMG points: 9P and 0B. PM1PM2PP3_StrongPP5
The NM_000274.4(OAT):c.162C>A(p.Asn54Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,614,086 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). Synonymous variant affecting the same amino acid position (i.e. N54N) has been classified as Likely benign.
Frequency
Consequence
NM_000274.4 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 | UniProt |
---|---|---|---|---|---|---|---|
OAT | NM_000274.4 | c.162C>A | p.Asn54Lys | missense_variant | 2/10 | ENST00000368845.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OAT | ENST00000368845.6 | c.162C>A | p.Asn54Lys | missense_variant | 2/10 | 1 | NM_000274.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251486Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461866Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727236
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74364
ClinVar
Submissions by phenotype
Ornithine aminotransferase deficiency Pathogenic:2Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 20, 2022 | This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 54 of the OAT protein (p.Asn54Lys). This variant is present in population databases (rs121965048, gnomAD 0.003%). This missense change has been observed in individual(s) with gyrate atrophy (PMID: 3375240). ClinVar contains an entry for this variant (Variation ID: 163). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects OAT function (PMID: 3375240). 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. - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 1988 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 13, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at