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NM_000531.6(OTC):c.78-1G>T AND Ornithine carbamoyltransferase deficiency

Clinical significance:Likely pathogenic (Last evaluated: Aug 12, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

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Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001994992.4

Allele description [Variation Report for NM_000531.6(OTC):c.78-1G>T]

NM_000531.6(OTC):c.78-1G>T

Gene:
OTC:ornithine transcarbamylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp11.4
Genomic location:
Preferred name:
NM_000531.6(OTC):c.78-1G>T
HGVS:
  • NC_000023.11:g.38367290G>T
  • NG_008471.1:g.19808G>T
  • NM_000531.6:c.78-1G>TMANE SELECT
  • LRG_846t1:c.78-1G>T
  • LRG_846:g.19808G>T
  • NC_000023.10:g.38226543G>T
Molecular consequence:
  • NM_000531.6:c.78-1G>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Ornithine carbamoyltransferase deficiency (OTCD)
Synonyms:
ORNITHINE TRANSCARBAMYLASE DEFICIENCY, HYPERAMMONEMIA DUE TO; Ornithine transcarbamylase deficiency; OTC deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010703; MedGen: C0268542; Orphanet: 664; OMIM: 311250

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002248791Invitaecriteria provided, single submitter
Likely pathogenic
(Aug 12, 2021) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Genotype spectrum of ornithine transcarbamylase deficiency: correlation with the clinical and biochemical phenotype.

McCullough BA, Yudkoff M, Batshaw ML, Wilson JM, Raper SE, Tuchman M.

Am J Med Genet. 2000 Aug 14;93(4):313-9.

PubMed [citation]
PMID:
10946359
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002248791.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 1 of the OTC gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OTC are known to be pathogenic (PMID: 10946359, 16786505). This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with OTC-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 7, 2023