ClinVar Genomic variation as it relates to human health
NM_000274.4(OAT):c.1186C>T (p.Arg396Ter)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000274.4(OAT):c.1186C>T (p.Arg396Ter)
Variation ID: 149 Accession: VCV000000149.10
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 10q26.13 10: 124398076 (GRCh38) [ NCBI UCSC ] 10: 126086645 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 23, 2016 Feb 14, 2024 Aug 25, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000274.4:c.1186C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000265.1:p.Arg396Ter nonsense NM_001171814.2:c.772C>T NP_001165285.1:p.Arg258Ter nonsense NM_001322965.2:c.1186C>T NP_001309894.1:p.Arg396Ter nonsense NM_001322966.2:c.1186C>T NP_001309895.1:p.Arg396Ter nonsense NM_001322967.2:c.1186C>T NP_001309896.1:p.Arg396Ter nonsense NM_001322968.2:c.1186C>T NP_001309897.1:p.Arg396Ter nonsense NM_001322969.2:c.1186C>T NP_001309898.1:p.Arg396Ter nonsense NM_001322970.2:c.1186C>T NP_001309899.1:p.Arg396Ter nonsense NM_001322971.2:c.865C>T NP_001309900.1:p.Arg289Ter nonsense NM_001322974.2:c.586C>T NP_001309903.1:p.Arg196Ter nonsense NC_000010.11:g.124398076G>A NC_000010.10:g.126086645G>A NG_008861.1:g.25875C>T LRG_685:g.25875C>T LRG_685t1:c.1186C>T LRG_685p1:p.Arg396Ter - Protein change
- R396*, R258*, R196*, R289*
- Other names
- -
- Canonical SPDI
- NC_000010.11:124398075:G:A
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
-
-
Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
---|---|---|---|---|---|---|
HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
|||
OAT | - | - |
GRCh38 GRCh37 |
579 | 690 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
---|---|---|---|---|
Pathogenic (3) |
criteria provided, multiple submitters, no conflicts
|
Aug 25, 2023 | RCV000000172.11 | |
Likely pathogenic (1) |
criteria provided, single submitter
|
Sep 28, 2018 | RCV000760452.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
|
---|---|---|---|---|---|
Likely pathogenic
(Sep 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000890338.1
First in ClinVar: Mar 19, 2019 Last updated: Mar 19, 2019 |
Comment:
The R396X variant in the OAT gene has been reported previously in the homozygous state in an individual with gyrate atrophy (Brody et al., 1992). … (more)
The R396X variant in the OAT gene has been reported previously in the homozygous state in an individual with gyrate atrophy (Brody et al., 1992). This variant is predicted to cause loss of normal protein function through protein truncation as the last 44 amino acids are lost. The R396X variant is not observed in large population cohorts (Lek et al., 2016). We interpret R396X as a likely pathogenic variant. (less)
|
|
Pathogenic
(Aug 25, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Ornithine aminotransferase deficiency
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004192219.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
|
|
Pathogenic
(Jul 13, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Ornithine aminotransferase deficiency
Affected status: unknown
Allele origin:
germline
|
Invitae
Accession: SCV001394493.5
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg396*) in the OAT gene. While this is not anticipated to result in nonsense mediated decay, … (more)
This sequence change creates a premature translational stop signal (p.Arg396*) in the OAT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 44 amino acid(s) of the OAT protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with gyrate atrophy (PMID: 1737786). ClinVar contains an entry for this variant (Variation ID: 149). This variant disrupts a region of the OAT protein in which other variant(s) (p.Arg426*) have been determined to be pathogenic (PMID: 7887415, 23076989). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
Pathogenic
(Feb 15, 1992)
|
no assertion criteria provided
Method: literature only
|
GYRATE ATROPHY OF CHOROID AND RETINA
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000020315.2
First in ClinVar: Apr 04, 2013 Last updated: Oct 23, 2016 |
Comment on evidence:
An East Indian patient with gyrate atrophy of the choroid and retina (258870) was found to be homozygous for a C-to-T transition at nucleotide 1186 … (more)
An East Indian patient with gyrate atrophy of the choroid and retina (258870) was found to be homozygous for a C-to-T transition at nucleotide 1186 of the OAT gene, resulting in an arg396-to-ter (R396X) substitution (Mitchell et al., 1989; Brody et al., 1992). (less)
|
Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
---|---|---|---|---|
Functional analysis of missense mutations of OAT, causing gyrate atrophy of choroid and retina. | Doimo M | Human mutation | 2013 | PMID: 23076989 |
Pyridoxine-responsive gyrate atrophy of the choroid and retina: clinical and biochemical correlates of the mutation A226V. | Michaud J | American journal of human genetics | 1995 | PMID: 7887415 |
Ornithine delta-aminotransferase mutations in gyrate atrophy. Allelic heterogeneity and functional consequences. | Brody LC | The Journal of biological chemistry | 1992 | PMID: 1737786 |
An initiator codon mutation in ornithine-delta-aminotransferase causing gyrate atrophy of the choroid and retina. | Mitchell GA | The Journal of clinical investigation | 1988 | PMID: 3339136 |
Text-mined citations for rs121965036 ...
HelpRecord last updated Feb 14, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.