NM_000274.4(OAT):c.533G>A (p.Trp178Ter) AND Ornithine aminotransferase deficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 8, 2023
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:: RCV000000202.5

Allele description [Variation Report for NM_000274.4(OAT):c.533G>A (p.Trp178Ter)]

NM_000274.4(OAT):c.533G>A (p.Trp178Ter)

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.533G>A (p.Trp178Ter)

HGVS:

NC_000010.11:g.124405551C>T
NG_008861.1:g.18400G>A
NM_000274.4:c.533G>AMANE SELECT
NM_001171814.2:c.119G>A
NM_001322965.2:c.533G>A
NM_001322966.2:c.533G>A
NM_001322967.2:c.533G>A
NM_001322968.2:c.533G>A
NM_001322969.2:c.533G>A
NM_001322970.2:c.533G>A
NM_001322971.2:c.212G>A
NM_001322974.2:c.-68G>A
NP_000265.1:p.Trp178Ter
NP_001165285.1:p.Trp40Ter
NP_001309894.1:p.Trp178Ter
NP_001309895.1:p.Trp178Ter
NP_001309896.1:p.Trp178Ter
NP_001309897.1:p.Trp178Ter
NP_001309898.1:p.Trp178Ter
NP_001309899.1:p.Trp178Ter
NP_001309900.1:p.Trp71Ter
LRG_685:g.18400G>A
NC_000010.10:g.126094120C>T

Protein change:

W178*; TRP178TER

Links:

OMIM: 613349.0036; dbSNP: rs267606923

NCBI 1000 Genomes Browser:

rs267606923

Molecular consequence:

NM_001322974.2:c.-68G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000274.4:c.533G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001171814.2:c.119G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322965.2:c.533G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322966.2:c.533G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322967.2:c.533G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322968.2:c.533G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322969.2:c.533G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322970.2:c.533G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001322971.2:c.212G>A - 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

Recent activity

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retinoic acid receptor alpha isoform b [Rattus norvegicus]
retinoic acid receptor alpha isoform b [Rattus norvegicus]
gi|158262026|ref|NP_113716.2|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000020345	OMIM	no assertion criteria provided	Pathogenic (Jan 29, 1993)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV004616210	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 8, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 1737786, 23076989, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000020345

OMIM

no assertion criteria provided

Pathogenic
(Jan 29, 1993)

germline

literature only

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

SCV004616210

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 8, 2023)

germline

clinical testing

PubMed (3)
[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

The skipping of constitutive exons in vivo induced by nonsense mutations.

Dietz HC, Valle D, Francomano CA, Kendzior RJ Jr, Pyeritz RE, Cutting GR.

Science. 1993 Jan 29;259(5095):680-3.

PubMed [citation]

PMID:: 8430317

Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences.

Brody LC, Mitchell GA, Obie C, Michaud J, Steel G, Fontaine G, Robert MF, Sipila I, Kaiser-Kupfer M, Valle D.

J Biol Chem. 1992 Feb 15;267(5):3302-7.

PubMed [citation]

PMID:: 1737786

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000020345.2

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

Description

Dietz et al. (1993) found deletion of exon 6 of the OAT gene in a patient with gyrate atrophy of the choroid and retina (GACR; 258870). The basis of the deletion was shown to be a nonsense mutation at codon 178 within the skipped exon. The patient was homozygous for a G-to-A transition at position +13 of exon 6 (W178X). See 613349.0031 for another example of skipping of exon 6 in a patient with gyrate atrophy of the choroid and retina.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004616210.1

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 179). This variant has not been reported in the literature in individuals affected with OAT-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp178*) in the OAT gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in OAT are known to be pathogenic (PMID: 1737786, 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

Last Updated: Sep 29, 2024

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