Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_000531.6(OTC):c.42del (p.Phe14fs)

CA224593

97194 (ClinVar)

Gene: OTC (HGNC:5009)
Condition: ornithine carbamoyltransferase deficiency (MONDO:0010703)
Inheritance Mode: X-linked inheritance
UUID: 9d6f02c6-831e-44b8-9349-2a7fc5e88e20
Approved on: 2026-05-19
Published on: 2026-09-10

HGVS expressions

NM_000531.6:c.42del
NM_000531.6(OTC):c.42del (p.Phe14fs)
NC_000023.11:g.38352738del
CM000685.2:g.38352738del
NC_000023.10:g.38211991del
CM000685.1:g.38211991del
NC_000023.9:g.38096935del
NG_008471.1:g.5256del
ENST00000039007.5:c.42del
ENST00000643344.1:c.42del
ENST00000039007.4:c.42del
ENST00000465127.1:c.172-313383del
ENST00000488812.1:n.134del
NM_000531.5:c.42del
More

Pathogenic

Met criteria codes 3
PP4_Moderate PM2_Supporting PVS1
Not Met criteria codes 2
BA1 BS1

Evidence Links 0

Expert Panel

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.42del (p.Phe14LeufsTer24) variant in OTC is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 1/10 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1; GeneReviews). At least one heterozygous female individual with this variant displayed elevated ammonia, low/normal citrulline and elevated urine orotic acid, which is highly specific for Ornitine Transcarbamilase (PP4_Moderate, PMID:14976564). This variant is absent from gnomAD v41.0 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for X-linked ornithine carbamoyltransferase deficiency. ACMG/AMP criteria met, as specified by the ClinGen Urea Cycle Disorders VCEP (OTC specifications version 1.0.0): PVS1, PP4_Moderate, PM2_Supporting
Met criteria codes
PP4_Moderate
At least one heterozygous female individual with this variant displayed elevated ammonia, low/normal citrulline and elevated urine orotic acid, which is highly specific for Ornitine Transcarbamilase (PP4_Moderate, PMID:14976564).
PM2_Supporting
This variant is absent in gnomAD v4.1.0 (PM2_Supporting).
PVS1
The NM_000531.6:c.42del (p.Phe14LeufsTer24) variant in OTC is a frameshift variant predicted to cause a premature stop codon in biologically relevant exon 1/10 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1)
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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