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.137A>G (p.Lys46Arg)

CA121291

10994 (ClinVar)

Gene: OTC (HGNC:5009)

Condition: ornithine carbamoyltransferase deficiency (MONDO:0010703)

Inheritance Mode: X-linked inheritance

UUID: 49573b1f-663f-4820-99c1-cd9eeebbc98e

Approved on: 2026-06-11

Published on: 2026-09-11

HGVS expressions

NM_000531.6:c.137A>G

NM_000531.6(OTC):c.137A>G (p.Lys46Arg)

NC_000023.11:g.38367350A>G

CM000685.2:g.38367350A>G

NC_000023.10:g.38226603A>G

CM000685.1:g.38226603A>G

NC_000023.9:g.38111547A>G

NG_008471.1:g.19868A>G

ENST00000039007.5:c.137A>G

ENST00000643344.1:c.137A>G

ENST00000039007.4:c.137A>G

ENST00000465127.1:c.172-298771A>G

ENST00000488812.1:n.229A>G

NM_000531.5:c.137A>G

Benign

BA1

PP3 PM1 BP4

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:c.137A>G (p.Lys46Arg) is a missense OTC variant in exon 2. The MAF >5% in all populations except in East Asians with more than one hundred thousand combined homo- and hemizygotes (BA1). In summary, this variant meets the criteria to be classified as benign 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): BA1.

BA1

The frequency of the G allele is >1% in all populations except in East Asians, and has combined homo-/hemizygotes over one hundred thousand. BA1 applies per OTC-specific criteria established by the UCD VCEP.

PP3

REVEL score of 0.407 is lower than the 0.644 threshold for PP3 but higher than the OTC gene-specific 0.290 cut-off for BP4.

PM1

Not in any of the designated hotspots per the OTC specifications

BP4

REVEL score of 0.407 is lower than the 0.644 threshold for PP3 but higher than the OTC gene-specific 0.290 cut-off for BP4.

Curation History

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