NM_000274.4(OAT):c.1118G>A (p.Gly373Glu) AND Ornithine aminotransferase deficiency

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Aug 22, 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:: RCV000049521.4

Allele description [Variation Report for NM_000274.4(OAT):c.1118G>A (p.Gly373Glu)]

NM_000274.4(OAT):c.1118G>A (p.Gly373Glu)

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.1118G>A (p.Gly373Glu)

HGVS:

NC_000010.11:g.124400881C>T
NG_008861.1:g.23070G>A
NM_000274.4:c.1118G>AMANE SELECT
NM_001171814.2:c.704G>A
NM_001322965.2:c.1118G>A
NM_001322966.2:c.1118G>A
NM_001322967.2:c.1118G>A
NM_001322968.2:c.1118G>A
NM_001322969.2:c.1118G>A
NM_001322970.2:c.1118G>A
NM_001322971.2:c.797G>A
NM_001322974.2:c.518G>A
NP_000265.1:p.Gly373Glu
NP_000265.1:p.Gly373Glu
NP_001165285.1:p.Gly235Glu
NP_001309894.1:p.Gly373Glu
NP_001309895.1:p.Gly373Glu
NP_001309896.1:p.Gly373Glu
NP_001309897.1:p.Gly373Glu
NP_001309898.1:p.Gly373Glu
NP_001309899.1:p.Gly373Glu
NP_001309900.1:p.Gly266Glu
NP_001309903.1:p.Gly173Glu
LRG_685t1:c.1118G>A
LRG_685:g.23070G>A
LRG_685p1:p.Gly373Glu
NC_000010.10:g.126089450C>T
NM_000274.3:c.1118G>A

Protein change:

G173E

Links:

dbSNP: rs386833595

NCBI 1000 Genomes Browser:

rs386833595

Molecular consequence:

NM_000274.4:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001171814.2:c.704G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322965.2:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322966.2:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322967.2:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322968.2:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322969.2:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322970.2:c.1118G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322971.2:c.797G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322974.2:c.518G>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
SCV000081957	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]
SCV002214137	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 1609808, 28492532
SCV002812214	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 21, 2021)	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

SCV000081957

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]

SCV002214137

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 22, 2022)

germline

clinical testing

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

SCV002812214

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 21, 2021)

unknown

clinical testing

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

Description

FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference: SCV000081957

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	unknown	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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000081957.1

#	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 Invitae, SCV002214137.2

#	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 glutamic acid, which is acidic and polar, at codon 373 of the OAT protein (p.Gly373Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with gyrate atrophy of the choroid and retina (PMID: 1609808). ClinVar contains an entry for this variant (Variation ID: 56112). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Fulgent Genetics, Fulgent Genetics, SCV002812214.1

#	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 7, 2023

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