rs72558470
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PM1PM2PM5PP3_StrongPP5_Moderate
The NM_000531.6(OTC):c.943G>T(p.Val315Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V315A) has been classified as Pathogenic.
Frequency
Consequence
NM_000531.6 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 |
---|---|---|---|---|---|---|---|
OTC | NM_000531.6 | c.943G>T | p.Val315Phe | missense_variant | 9/10 | ENST00000039007.5 | |
OTC | NM_001407092.1 | c.943G>T | p.Val315Phe | missense_variant | 11/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTC | ENST00000039007.5 | c.943G>T | p.Val315Phe | missense_variant | 9/10 | 1 | NM_000531.6 | P1 | |
OTC | ENST00000643344.1 | c.*693G>T | 3_prime_UTR_variant, NMD_transcript_variant | 10/11 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD4 exome Cov.: 29
GnomAD4 genome ? Cov.: 23
ClinVar
Submissions by phenotype
Ornithine carbamoyltransferase deficiency Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Sep 20, 2016 | Variant summary: The OTC c.943G>T (p.Val315Phe) variant involves the alteration of a conserved nucleotide. Val315 is located in the Aspartate/ornithine carbamoyltransferase, Asp/Orn-binding domain (InterPro). 5/5 in silico tools predict a damaging outcome for this variant. This variant is absent in 87705 control chromosomes. p.Val315Gly and p.Val315Asp have been classified as pathogenic in ClinVar and HGMD, suggesting Val315 is critical for the function of OTC protein. In addition, one clinical diagnostic laboratory/reputable database has classified this variant as pathogenic. Taken together, this variant is classified as likely pathogenic until additional data becomes available (occurrences in OTCD patients and functional studies). - |
not provided Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | GenMed Metabolism Lab | - | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at