rs72558487
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PM5BS2
The NM_000531.6(OTC):c.1009G>A(p.Val337Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000184 in 1,084,196 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. 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. V337L) has been classified as Pathogenic.
Frequency
Consequence
NM_000531.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTC | NM_000531.6 | c.1009G>A | p.Val337Ile | missense_variant | 10/10 | ENST00000039007.5 | |
OTC | NM_001407092.1 | c.1009G>A | p.Val337Ile | missense_variant | 12/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | c.1009G>A | p.Val337Ile | missense_variant | 10/10 | 1 | NM_000531.6 | P1 | |
OTC | ENST00000643344.1 | c.*759G>A | 3_prime_UTR_variant, NMD_transcript_variant | 11/11 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome AF: 0.00000184 AC: 2AN: 1084196Hom.: 0 Cov.: 26 AF XY: 0.00000570 AC XY: 2AN XY: 351094
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Ornithine carbamoyltransferase deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Aug 23, 2023 | This missense variant replaces valine with isoleucine at codon 337 of the OTC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with OTC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at