NM_000531.6(OTC):c.460G>T (p.Glu154Ter) AND Ornithine carbamoyltransferase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Sep 26, 2021
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:: RCV000011738.15

Allele description [Variation Report for NM_000531.6(OTC):c.460G>T (p.Glu154Ter)]

NM_000531.6(OTC):c.460G>T (p.Glu154Ter)

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.460G>T (p.Glu154Ter)

HGVS:

NC_000023.11:g.38401348G>T
NG_008471.1:g.53866G>T
NM_000531.6:c.460G>TMANE SELECT
NP_000522.3:p.Glu154Ter
LRG_846t1:c.460G>T
LRG_846:g.53866G>T
LRG_846p1:p.Glu154Ter
NC_000023.10:g.38260601G>T
NM_000531.5:c.460G>T

Protein change:

E154*; GLU154TER

Links:

OMIM: 300461.0006; dbSNP: rs72556267

NCBI 1000 Genomes Browser:

rs72556267

Molecular consequence:

NM_000531.6:c.460G>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000031970	OMIM	no assertion criteria provided	Pathogenic (Aug 1, 1989)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002221689	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 26, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 2474822, 10946359, 16786505, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000031970

OMIM

no assertion criteria provided

Pathogenic
(Aug 1, 1989)

germline

literature only

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

SCV002221689

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 26, 2021)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Scanning detection of mutations in human ornithine transcarbamoylase by chemical mismatch cleavage.

Grompe M, Muzny DM, Caskey CT.

Proc Natl Acad Sci U S A. 1989 Aug;86(15):5888-92.

PubMed [citation]

PMID:: 2474822
PMCID:: PMC297736

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 OMIM, SCV000031970.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a patient with OTC deficiency (311250), Grompe et al. (1989) identified a nonsense mutation, glu154-to-ter (E154X).

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

From Invitae, SCV002221689.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 10991). This premature translational stop signal has been observed in individual(s) with ornithine transcarbamylase deficiency (PMID: 2474822). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu154*) in the OTC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OTC are known to be pathogenic (PMID: 10946359, 16786505).

#	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

Last Updated: Feb 14, 2024

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