NM_000274.4(OAT):c.1201G>T (p.Gly401Ter) AND Ornithine aminotransferase deficiency

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 17, 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:: RCV000000196.9

Allele description [Variation Report for NM_000274.4(OAT):c.1201G>T (p.Gly401Ter)]

NM_000274.4(OAT):c.1201G>T (p.Gly401Ter)

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.1201G>T (p.Gly401Ter)

HGVS:

NC_000010.11:g.124398061C>A
NG_008861.1:g.25890G>T
NM_000274.4:c.1201G>TMANE SELECT
NM_001171814.2:c.787G>T
NM_001322965.2:c.1201G>T
NM_001322966.2:c.1201G>T
NM_001322967.2:c.1201G>T
NM_001322968.2:c.1201G>T
NM_001322969.2:c.1201G>T
NM_001322970.2:c.1201G>T
NM_001322971.2:c.880G>T
NM_001322974.2:c.601G>T
NP_000265.1:p.Gly401Ter
NP_001165285.1:p.Gly263Ter
NP_001309894.1:p.Gly401Ter
NP_001309895.1:p.Gly401Ter
NP_001309896.1:p.Gly401Ter
NP_001309897.1:p.Gly401Ter
NP_001309898.1:p.Gly401Ter
NP_001309899.1:p.Gly401Ter
NP_001309900.1:p.Gly294Ter
NP_001309903.1:p.Gly201Ter
LRG_685:g.25890G>T
NC_000010.10:g.126086630C>A

Protein change:

G201*; GLY401TER

Links:

OMIM: 613349.0030; dbSNP: rs121965055

NCBI 1000 Genomes Browser:

rs121965055

Molecular consequence:

NM_000274.4:c.1201G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001171814.2:c.787G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322965.2:c.1201G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322966.2:c.1201G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322967.2:c.1201G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322968.2:c.1201G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322969.2:c.1201G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322970.2:c.1201G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322971.2:c.880G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322974.2:c.601G>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
SCV000020339	OMIM	no assertion criteria provided	Pathogenic (Jun 1, 1992)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002142015	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 16, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 1609808, 24429551, 23076989, 1737786, 28492532
SCV004208954	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 17, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000020339

OMIM

no assertion criteria provided

Pathogenic
(Jun 1, 1992)

germline

literature only

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

SCV002142015

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 16, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004208954

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jan 17, 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	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
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Strand-separating conformational polymorphism analysis: efficacy of detection of point mutations in the human ornithine delta-aminotransferase gene.

Michaud J, Brody LC, Steel G, Fontaine G, Martin LS, Valle D, Mitchell G.

Genomics. 1992 Jun;13(2):389-94.

PubMed [citation]

PMID:: 1612597

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

See all PubMed Citations (7)

Details of each submission

From OMIM, SCV000020339.2

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

Description

Using SSCP analysis, Michaud et al. (1992) demonstrated a G-to-T transversion at nucleotide 1201 of the OAT mRNA, changing glycine-401 to a stop codon (G401X) in a patient with gyrate atrophy of the choroid and retina (GACR; 258870).

#	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, SCV002142015.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This variant disrupts the C-terminus of the OAT protein. Other variant(s) that disrupt this region (p.Arg426*) have been determined to be pathogenic (PMID: 1609808, 24429551, 23076989). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with gyrate atrophy (PMID: 1737786). ClinVar contains an entry for this variant (Variation ID: 173). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gly401*) in the OAT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 39 amino acid(s) of the OAT protein.

#	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 Baylor Genetics, SCV004208954.1

#	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: Feb 14, 2024

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