NM_000274.4(OAT):c.1276C>T (p.Arg426Ter) AND Hyperornithinemia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 14, 2022
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:: RCV002271362.8

Allele description [Variation Report for NM_000274.4(OAT):c.1276C>T (p.Arg426Ter)]

NM_000274.4(OAT):c.1276C>T (p.Arg426Ter)

Gene:

OAT:ornithine aminotransferase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q26.13

Genomic location:

Preferred name:

NM_000274.4(OAT):c.1276C>T (p.Arg426Ter)

HGVS:

NC_000010.11:g.124397986G>A
NG_008861.1:g.25965C>T
NM_000274.4:c.1276C>TMANE SELECT
NM_001171814.2:c.862C>T
NM_001322965.2:c.1276C>T
NM_001322966.2:c.1276C>T
NM_001322967.2:c.1276C>T
NM_001322968.2:c.1276C>T
NM_001322969.2:c.1276C>T
NM_001322970.2:c.1276C>T
NM_001322971.2:c.955C>T
NM_001322974.2:c.676C>T
NP_000265.1:p.Arg426Ter
NP_000265.1:p.Arg426Ter
NP_001165285.1:p.Arg288Ter
NP_001309894.1:p.Arg426Ter
NP_001309895.1:p.Arg426Ter
NP_001309896.1:p.Arg426Ter
NP_001309897.1:p.Arg426Ter
NP_001309898.1:p.Arg426Ter
NP_001309899.1:p.Arg426Ter
NP_001309900.1:p.Arg319Ter
NP_001309903.1:p.Arg226Ter
LRG_685t1:c.1276C>T
LRG_685:g.25965C>T
LRG_685p1:p.Arg426Ter
NC_000010.10:g.126086555G>A
NM_000274.3:c.1276C>T

Protein change:

R226*; ARG426TER

Links:

OMIM: 613349.0034; dbSNP: rs121965058

NCBI 1000 Genomes Browser:

rs121965058

Molecular consequence:

NM_000274.4:c.1276C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001171814.2:c.862C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322965.2:c.1276C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322966.2:c.1276C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322967.2:c.1276C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322968.2:c.1276C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322969.2:c.1276C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322970.2:c.1276C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322971.2:c.955C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322974.2:c.676C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hyperornithinemia
Synonyms:: Ornithinemia
Identifiers:: MedGen: C0599035; Human Phenotype Ontology: HP:0012026

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002555863	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Jun 14, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 23076989, 24429551, 8125717 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002555863

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Jun 14, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Functional analysis of missense mutations of OAT, causing gyrate atrophy of choroid and retina.

Doimo M, Desbats MA, Baldoin MC, Lenzini E, Basso G, Murphy E, Graziano C, Seri M, Burlina A, Sartori G, Trevisson E, Salviati L.

Hum Mutat. 2013 Jan;34(1):229-36. doi: 10.1002/humu.22233. Epub 2012 Oct 17.

PubMed [citation]

PMID:: 23076989

OAT mutations and clinical features in two Japanese brothers with gyrate atrophy of the choroid and retina.

Katagiri S, Gekka T, Hayashi T, Ida H, Ohashi T, Eto Y, Tsuneoka H.

Doc Ophthalmol. 2014 Apr;128(2):137-48. doi: 10.1007/s10633-014-9426-1. Epub 2014 Jan 16.

PubMed [citation]

PMID:: 24429551

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002555863.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

Variant summary: OAT c.1276C>T (p.Arg426X) results in a premature termination codon in the last exon of the protein, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 250712 control chromosomes (gnomAD). c.1276C>T has been reported in the literature in homozygous and compound heterozygous individuals affected with Ornithine Aminotransferase Deficiency (examples: Katagiri_2014 and Mashima_1994). These data indicate that the variant is very likely to be associated with disease. In yeast this variant effect results in <10% of normal activity (Doimo_2012). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#	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: May 19, 2024

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