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:c.147C>T

CA10385792

1166654 (ClinVar)

Gene: OTC (HGNC:5009)

Condition: ornithine carbamoyltransferase deficiency (MONDO:0010703)

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

UUID: e4b0d0d7-3c7f-41b8-aebf-49a2babb1955

Approved on: 2026-05-20

Published on: 2026-05-29

HGVS expressions

NM_000531.6:c.147C>T

NC_000023.11:g.38367360C>T

CM000685.2:g.38367360C>T

NC_000023.10:g.38226613C>T

CM000685.1:g.38226613C>T

NC_000023.9:g.38111557C>T

NG_008471.1:g.19878C>T

ENST00000039007.5:c.147C>T

ENST00000643344.1:c.147C>T

ENST00000039007.4:c.147C>T

ENST00000465127.1:c.172-298761C>T

ENST00000488812.1:n.239C>T

NM_000531.5:c.147C>T

Benign

BA1 BP7 BP4

PM1

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.147C>T (p.Thr49=) variant in OTC is a synonymous variant in exon 2 of the OTC gene. There are 10 hemizygous males in gnomAD v.4.1.0. This variant being observed in ≥10 (female) homozygotes or (male) hemizygotes in the most current version of gnomAD available at the time of curation (v.4.1.0), The NM_000531.6:c.147C>T (p.Thr49=) meets BP4 (Splice AI predicts no impact of the variant on splicing) (BP4, BP7) In summary, this variant meets the criteria to be classified as a benign variant 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, BP4, BP7

BA1

There are 10 hemizygous males in gnomAD v.4.1.0. This variant being observed in ≥10 (female) homozygotes or (male) hemizygotes in the most current version of gnomAD available at the time of curation (v.4.1.0) is an OTC-specific stand-alone criterion for benign variants. As a result, this variant meets this criterion (BA1).

BP7

SpliceAI predicts no impact on splicing (scores <0.2) and nucleotide is not highly conserved (conservation score in the Cactus alignment of 447 mammalian genomes is -3.147).

BP4

The NM_000531.6:c.147C>T (p.Thr49=) meets BP4 (Splice AI predicts no impact of the variant on splicing) and the nucleotide is poorly conserved (Cactus 447 phyloP score -3.147).

PM1

This variant is not located in a mutational hot spot and/or critical and well-established functional domain (e.g. active site of an enzyme) in OTC.

Curation History

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