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NM_000531.6(OTC):c.298+1G>A AND Ornithine carbamoyltransferase deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 8, 2017
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000560147.6

Allele description [Variation Report for NM_000531.6(OTC):c.298+1G>A]

NM_000531.6(OTC):c.298+1G>A

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.298+1G>A
HGVS:
  • NC_000023.11:g.38369878G>A
  • NG_008471.1:g.22396G>A
  • NM_000531.6:c.298+1G>AMANE SELECT
  • NM_001407092.1:c.298+1G>A
  • LRG_846t1:c.298+1G>A
  • LRG_846:g.22396G>A
  • NC_000023.10:g.38229131G>A
  • NM_000531.5:c.298+1G>A
Links:
dbSNP: rs68058881
NCBI 1000 Genomes Browser:
rs68058881
Molecular consequence:
  • NM_000531.6:c.298+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001407092.1:c.298+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000631858Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jun 8, 2017) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutations and polymorphisms in the human ornithine transcarbamylase (OTC) gene.

Yamaguchi S, Brailey LL, Morizono H, Bale AE, Tuchman M.

Hum Mutat. 2006 Jul;27(7):626-32.

PubMed [citation]
PMID:
16786505

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
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000631858.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Two different variants affecting this nucleotide (c.298+1G>C, c.298+1G>T) have been determined to be pathogenic (PMID: 16786505, 25433810). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in OTC are known to be pathogenic (PMID: 10946359). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been reported in an individual affected with ornithine transcarbamylase deficiency (PMID: 8530002). ClinVar contains an entry for this variant (Variation ID: 97159). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 3 of the OTC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

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

Last Updated: Sep 29, 2024