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.621C>T (p.Ser207=)

CA10385896

368259 (ClinVar)

Gene: OTC (HGNC:5009)

Condition: ornithine carbamoyltransferase deficiency (MONDO:0010703)

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

UUID: 412b662e-dec2-45af-ba81-64507e94994c

Approved on: 2026-05-21

Published on: 2026-05-29

HGVS expressions

NM_000531.6(OTC):c.621C>T (p.Ser207=)

NM_000531.6:c.621C>T

NC_000023.11:g.38403698C>T

CM000685.2:g.38403698C>T

NC_000023.10:g.38262951C>T

CM000685.1:g.38262951C>T

NC_000023.9:g.38147895C>T

NG_008471.1:g.56216C>T

ENST00000039007.5:c.621C>T

ENST00000643344.1:c.*371C>T

ENST00000039007.4:c.621C>T

ENST00000465127.1:c.172-262423C>T

NM_000531.5:c.621C>T

Benign

BP7 BA1

PM1 PM2 PP4

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.621C>T (p.Ser207=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing (BP4, BP7). The highest population minor allele frequency in gnomAD v4.1.0 is 0.0008888 (30/33752 alleles) in the East Asian population and there are 13 hemizygotes across all populations, which is higher than the ClinGen OTC VCEP threshold (≥10 male hemizygotes) for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign 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): BA1, BP4, BP7.

BP7

The c.621C>T (p.Ser207=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing (BP7). SpliceAI delta scores 0.00-0.01 (Donor Loss).

BA1

There are 13 total hemizygotes in gnomAD v4.1.0 which is higher than the ClinGen OTC VCEP threshold (≥10 male hemizygotes) for BA1, and therefore meets this criterion (BA1).

PM1

This variant is not at one of the well-established hotspots: Carbamoylphosphate binding site – amino acids: Ser-90, Thr-91, Arg-92, Thr-93, His-117, Arg-141, His-168 and Arg-330 Ornithine binding site – amino acids: Asn-199, Asp-263, Ser-267, Met-268, Gly-269 Catalytic site – amino acids: His-302, Cys-303, Leu-304, Pro-305 Salt bridge – Arg-92 and Glu-122

PM2

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PP4

Not reported in cases in the literature 4/8/23

Curation History

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