NM_000274.4(OAT):c.1276C>T (p.Arg426Ter) AND Ornithine aminotransferase deficiency

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Oct 18, 2023
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:: RCV000000200.19

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:: Ornithine aminotransferase deficiency (GACR)
Synonyms:: OAT deficiency; Ornithine ketoacid aminotransferase deficiency; Gyrate atrophy; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009796; MedGen: C0018425; Orphanet: 414; OMIM: 258870

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000020343	OMIM	no assertion criteria provided	Pathogenic (Jul 1, 1992)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001211238	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 29, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 1609808, 24429551, 23076989, 28492532
SCV002088028	Natera, Inc.	no assertion criteria provided	Pathogenic (Apr 9, 2021)	germline	clinical testing
SCV004030477	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 29, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004192206	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 18, 2023)	unknown	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	yes	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
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy.

Mashima Y, Murakami A, Weleber RG, Kennaway NG, Clarke L, Shiono T, Inana G.

Am J Hum Genet. 1992 Jul;51(1):81-91.

PubMed [citation]

PMID:: 1609808
PMCID:: PMC1682884

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 (5)

Details of each submission

From OMIM, SCV000020343.1

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

Description

See 613349.0032 and Mashima et al. (1992); the R426X mutation resulted from a homozygous C-to-T transition in exon 11.

#	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, SCV001211238.5

#	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. This sequence change creates a premature translational stop signal (p.Arg426*) in the OAT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 14 amino acid(s) of the OAT protein. This variant is present in population databases (rs121965058, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with gyrate atrophy (PMID: 1609808, 24429551). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 177). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects OAT function (PMID: 23076989).

#	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 Natera, Inc., SCV002088028.1

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

#	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 Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV004030477.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004192206.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 19, 2024

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