NM_000274.4(OAT):c.710G>A (p.Gly237Asp) AND Ornithine aminotransferase deficiency

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Nov 29, 2022
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:: RCV000049543.4

Allele description [Variation Report for NM_000274.4(OAT):c.710G>A (p.Gly237Asp)]

NM_000274.4(OAT):c.710G>A (p.Gly237Asp)

Genes:

LOC121815974:Sharpr-MPRA regulatory region 15365 [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.710G>A (p.Gly237Asp)

HGVS:

NC_000010.11:g.124403859C>T
NG_008861.1:g.20092G>A
NG_075868.1:g.420C>T
NM_000274.4:c.710G>AMANE SELECT
NM_001171814.2:c.296G>A
NM_001322965.2:c.710G>A
NM_001322966.2:c.710G>A
NM_001322967.2:c.710G>A
NM_001322968.2:c.710G>A
NM_001322969.2:c.710G>A
NM_001322970.2:c.710G>A
NM_001322971.2:c.389G>A
NM_001322974.2:c.110G>A
NP_000265.1:p.Gly237Asp
NP_000265.1:p.Gly237Asp
NP_001165285.1:p.Gly99Asp
NP_001309894.1:p.Gly237Asp
NP_001309895.1:p.Gly237Asp
NP_001309896.1:p.Gly237Asp
NP_001309897.1:p.Gly237Asp
NP_001309898.1:p.Gly237Asp
NP_001309899.1:p.Gly237Asp
NP_001309900.1:p.Gly130Asp
NP_001309903.1:p.Gly37Asp
LRG_685t1:c.710G>A
LRG_685:g.20092G>A
LRG_685p1:p.Gly237Asp
NC_000010.10:g.126092428C>T
NM_000274.3:c.710G>A

Protein change:

G130D

Links:

dbSNP: rs386833616

NCBI 1000 Genomes Browser:

rs386833616

Molecular consequence:

NM_000274.4:c.710G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171814.2:c.296G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322965.2:c.710G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322966.2:c.710G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322967.2:c.710G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322968.2:c.710G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322969.2:c.710G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322970.2:c.710G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322971.2:c.389G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322974.2:c.110G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000081980	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	no assertion criteria provided	probable-pathogenic	not provided	not provided	PubMed (1) [See all records that cite this PMID]
SCV004208959	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Aug 31, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004295742	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Nov 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 15750329, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000081980

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

no assertion criteria provided

probable-pathogenic

not provided

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

SCV004208959

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Aug 31, 2022)

unknown

clinical testing

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

SCV004295742

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Nov 29, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Description

FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference: SCV000081980

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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Vitamin B6-responsive ornithine aminotransferase deficiency with a novel mutation G237D.

Ohkubo Y, Ueta A, Ito T, Sumi S, Yamada M, Ozawa K, Togari H.

Tohoku J Exp Med. 2005 Apr;205(4):335-42.

PubMed [citation]

PMID:: 15750329

See all PubMed Citations (3)

Details of each submission

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000081980.1

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

Description

Converted during submission to Likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004208959.1

#	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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004295742.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 237 of the OAT protein (p.Gly237Asp). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt OAT protein function. ClinVar contains an entry for this variant (Variation ID: 56134). This missense change has been observed in individual(s) with gyrate atrophy of choroid and retina (PMID: 15750329). This variant is present in population databases (rs386833616, gnomAD 0.003%).

#	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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