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NM_000531.6(OTC):c.540+265G>A AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Mar 2, 2016
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:

Allele description [Variation Report for NM_000531.6(OTC):c.540+265G>A]


OTC:ornithine transcarbamylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
  • NC_000023.11:g.38401693G>A
  • NG_008471.1:g.54211G>A
  • NM_000531.6:c.540+265G>AMANE SELECT
  • LRG_846t1:c.540+265G>A
  • LRG_846:g.54211G>A
  • NC_000023.10:g.38260946G>A
  • NM_000531.5:c.540+265G>A
dbSNP: rs1555975756
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000531.6:c.540+265G>A - intron variant - [Sequence Ontology: SO:0001627]


none provided
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
criteria provided, single submitter

(GeneDx Variant Classification (06012015))
(Mar 2, 2016)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000617478.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


The c.540+265 G>A variant in the OTC gene has been reported previously in association with neonatal onset ornithine transcarbamylase (OTC) deficiency in hemizygous males (Ogino et al. 2007; Engel et al. 2008). mRNA analysis of c.540+265 G>A found that this variant results in an insertion of 135 bases in intron 5, creates a new splice acceptor site and leads to the creation of a new in-frame Stop codon, which causes loss of normal protein function through nonsense-mediated mRNA decay (Ogino et al. 2007; Engel et al. 2008). The c.540+265 G>A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. In summary, we interpret c.540+265 G>A to be a pathogenic variant, and its presence is consistent with the diagnosis of OTC deficiency in this individual. Approximately 20% of females who are heterozygous for variants in the OTC gene are clinically symptomatic with disease severity similar to males with partial deficiency (Yamaguchi et al., 2006; Tuchman et al., 2002).

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 7, 2024