NM_000274.4(OAT):c.1192C>T (p.Arg398Ter) AND Ornithine aminotransferase deficiency

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Mar 17, 2024
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:: RCV000542545.19

Allele description [Variation Report for NM_000274.4(OAT):c.1192C>T (p.Arg398Ter)]

NM_000274.4(OAT):c.1192C>T (p.Arg398Ter)

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.1192C>T (p.Arg398Ter)

HGVS:

NC_000010.11:g.124398070G>A
NG_008861.1:g.25881C>T
NM_000274.4:c.1192C>TMANE SELECT
NM_001171814.2:c.778C>T
NM_001322965.2:c.1192C>T
NM_001322966.2:c.1192C>T
NM_001322967.2:c.1192C>T
NM_001322968.2:c.1192C>T
NM_001322969.2:c.1192C>T
NM_001322970.2:c.1192C>T
NM_001322971.2:c.871C>T
NM_001322974.2:c.592C>T
NP_000265.1:p.Arg398Ter
NP_000265.1:p.Arg398Ter
NP_001165285.1:p.Arg260Ter
NP_001309894.1:p.Arg398Ter
NP_001309895.1:p.Arg398Ter
NP_001309896.1:p.Arg398Ter
NP_001309897.1:p.Arg398Ter
NP_001309898.1:p.Arg398Ter
NP_001309899.1:p.Arg398Ter
NP_001309900.1:p.Arg291Ter
NP_001309903.1:p.Arg198Ter
LRG_685t1:c.1192C>T
LRG_685:g.25881C>T
LRG_685p1:p.Arg398Ter
NC_000010.10:g.126086639G>A
NM_000274.3:c.1192C>T
NM_001322966.2:c.1192C>T

Protein change:

R198*

Links:

dbSNP: rs200068769

NCBI 1000 Genomes Browser:

rs200068769

Molecular consequence:

NM_000274.4:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001171814.2:c.778C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322965.2:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322966.2:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322967.2:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322968.2:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322969.2:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322970.2:c.1192C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322971.2:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322974.2:c.592C>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
SCV000626795	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 1, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 7887415, 23076989, 28492532
SCV002093801	Natera, Inc.	no assertion criteria provided	Pathogenic (Aug 18, 2020)	germline	clinical testing
SCV004048294	Neuberg Centre For Genomic Medicine, NCGM	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004192205	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 17, 2024)	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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
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

Citations

PubMed

Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V.

Michaud J, Thompson GN, Brody LC, Steel G, Obie C, Fontaine G, Schappert K, Keith CG, Valle D, Mitchell GA.

Am J Hum Genet. 1995 Mar;56(3):616-22.

PubMed [citation]

PMID:: 7887415
PMCID:: PMC1801175

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

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000626795.3

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

Description

This sequence change creates a premature translational stop signal (p.Arg398*) in the OAT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the OAT protein. This variant is present in population databases (rs200068769, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with gyrate atrophy of the choroid and the retina (PMID: 7887415). ClinVar contains an entry for this variant (Variation ID: 456519). 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: 7887415, 23076989). For these reasons, this variant has been 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

From Natera, Inc., SCV002093801.1

#	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 Neuberg Centre For Genomic Medicine, NCGM, SCV004048294.1

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

Description

The stop gained variant c.1192C>T (p.Arg398Ter) in OAT gene has been reported in an individual affected with gyrate atrophy of the choroid and the retina (Michaud J et.al.,1995). Experimental studies have shown that this nonsense change leads to a drastic reduction of the OAT enzymatic activity (Doimo M et.al.,2013). This variant has been reported to the ClinVar database as Pathogenic. The p.Arg398Ter variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.000797% is reported in gnomAD. The nucleotide change in OAT is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic

#	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, SCV004192205.2

#	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: Oct 13, 2024

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