Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000531.6(OTC):c.67C>T (p.Arg23Ter)

CA224742

97292 (ClinVar)

Gene: OTC (HGNC:5009)

Condition: ornithine carbamoyltransferase deficiency (MONDO:0010703)

Inheritance Mode: X-linked inheritance

UUID: c14edd18-22b7-4575-8a73-81897d3ea21e

Approved on: 2026-11-03

Published on: 2026-11-03

HGVS expressions

NM_000531.6(OTC):c.67C>T (p.Arg23Ter)

NM_000531.6:c.67C>T

NC_000023.11:g.38352763C>T

CM000685.2:g.38352763C>T

NC_000023.10:g.38212016C>T

CM000685.1:g.38212016C>T

NC_000023.9:g.38096960C>T

NG_008471.1:g.5281C>T

ENST00000039007.5:c.67C>T

ENST00000643344.1:c.67C>T

ENST00000039007.4:c.67C>T

ENST00000465127.1:c.172-313358C>T

ENST00000488812.1:n.159C>T

NM_000531.5:c.67C>T

Pathogenic

PVS1 PP4_Moderate PM2_Supporting

Evidence Links 0

Expert Panel

Urea Cycle Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Urea Cycle Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for OTC Version 1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Urea Cycle Disorders VCEP

The NM_000531.6(OTC):c.67C>T (p.Arg23Ter) variant in OTC is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 1 of OTC leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). One patient with this variant displayed Vomiting, Childhood onset, Hepatic failure, Hyperammonemia, Oroticaciduria, Elevated circulating alanine aminotransferase concentration, Lethargy, Elevated circulating uracil concentration, 4% OTC activity which is highly specific for OTC deficiency (3.25pts, PP4_Moderate, PMID: 24485820). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). In summary, this variant meets the criteria for being classified as Pathogenic for OTC deficiency. ACMG/AMP criteria applied, as specified by the ClinGen UCD VCEP Variant Interpretation Guidelines for OTC Version 1.0.0: PVS1, PM2_Supporting, PP4_Moderate

PVS1

The NM_000531.6(OTC):c.67C>T (p.Arg23Ter) variant in OTC is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 1 for OTC leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).

PP4_Moderate

One patient with this variant displayed Vomiting, Childhood onset, Hepatic failure, Hyperammonemia, Oroticaciduria, Elevated circulating alanine aminotransferase concentration, Lethargy, Elevated circulating uracil concentration, 4% OTC activity which is highly specific for OTC deficiency (3.25pts, PP4_Moderate, PMID: 24485820, Pathogenic).

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting)

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.