NM_000531.6(OTC):c.663+1G>T AND Ornithine carbamoyltransferase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 7, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000634848.7

Allele description [Variation Report for NM_000531.6(OTC):c.663+1G>T]

NM_000531.6(OTC):c.663+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.663+1G>T

HGVS:

NC_000023.11:g.38403741G>T
NG_008471.1:g.56259G>T
NM_000531.6:c.663+1G>TMANE SELECT
NM_001407092.1:c.663+1G>T
LRG_846t1:c.663+1G>T
LRG_846:g.56259G>T
NC_000023.10:g.38262994G>T
NM_000531.5:c.663+1G>T

Links:

dbSNP: rs68170503

NCBI 1000 Genomes Browser:

rs68170503

Molecular consequence:

NM_000531.6:c.663+1G>T - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001407092.1:c.663+1G>T - 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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000756197	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 27, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 10946359, 16786505, 8566955, 28492532
SCV002033226	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000756197

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 27, 2017)

germline

clinical testing

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

SCV002033226

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 7, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000756197.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

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, 16786505). 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 to be de novo in an individual affected with ornithine transcarbamylase (OTC) deficiency (PMID: 8566955). ClinVar contains an entry for this variant (Variation ID: 97284). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 6 of the OTC gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Genome-Nilou Lab, SCV002033226.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine