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.387T>C (p.Arg129_Val130=)

CA515650395

1915613 (ClinVar)

Gene: OTC (HGNC:5009)

Condition: ornithine carbamoyltransferase deficiency (MONDO:0010703)

Inheritance Mode: X-linked inheritance (recessive (HP:0001419))

UUID: c5b21332-3880-4e13-bf5a-ee895293b7c8

Approved on: 2026-05-21

Published on: 2026-05-29

HGVS expressions

NM_000531.6(OTC):c.387T>C (p.Arg129_Val130=)

NM_000531.6:c.387T>C

NC_000023.11:g.38401275T>C

CM000685.2:g.38401275T>C

NC_000023.10:g.38260528T>C

CM000685.1:g.38260528T>C

NC_000023.9:g.38145472T>C

NG_008471.1:g.53793T>C

ENST00000039007.5:c.387T>C

ENST00000643344.1:c.*137T>C

ENST00000039007.4:c.387T>C

ENST00000465127.1:c.172-264846T>C

ENST00000488812.1:n.424T>C

NM_000531.5:c.387T>C

Uncertain Significance

BP7 BP4 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 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Urea Cycle Disorders VCEP

The NM_000531.6:c.387T>C variant in OTC is a synonymous (silent) variant (p.Arg129_Val130=) that is not predicted by SpliceAI to impact splicing and the nucleotide (BP4), however the nucleotide is within the first 3 bases of an exon, so BP7 is not applicable. To our knowledge, this variant has not been reported in the literature and results of functional studies are unavailable. Grpmax MAF in gnomAD v4.1.0 is 0.000009190 in the European (non-Finnish) population which is lower than the ClinGen UCD VCEP’s threshold for PM2_Supporting (<0.000015) and there are ≤1 hemizygotes/homozygotes across all populations, meeting this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for OTC deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Urea Cycle Disorders Variant Curation Expert Panel (OTC specifications version 1.0.0): BP4, PM2_Supporting.

BP7

SpliceAI predicts no impact and nucleotide is not highly conserved.

BP4

The NM_000531.6(OTC):c.387T>C (p.Arg129_Val130=) meets BP4 (Splice AI predicts no impact of the on splicing) and the nucleotide is poorly conserved (phyloP score -0.107).

PM2_Supporting

Grpmax MAF in gnomAD v4.1.0 is 0.000009190 in the European (non-Finnish) population which is lower than the ClinGen UCD VCEP’s threshold for PM2_Supporting (<0.000015) and there are ≤1 hemizygotes/homozygotes across all populations, meeting this criterion (PM2_Supporting).

Curation History

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