ClinVar Genomic variation as it relates to human health
NM_000274.4(OAT):c.1192C>T (p.Arg398Ter)
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
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NM_000274.4(OAT):c.1192C>T (p.Arg398Ter)
Variation ID: 456519 Accession: VCV000456519.12
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q26.13 10: 124398070 (GRCh38) [ NCBI UCSC ] 10: 126086639 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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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 Dec 26, 2017 Jun 17, 2024 Mar 17, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000274.4:c.1192C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000265.1:p.Arg398Ter nonsense NM_001171814.2:c.778C>T NP_001165285.1:p.Arg260Ter nonsense NM_001322965.2:c.1192C>T NP_001309894.1:p.Arg398Ter nonsense NM_001322966.2:c.1192C>T NP_001309895.1:p.Arg398Ter nonsense NM_001322967.2:c.1192C>T NP_001309896.1:p.Arg398Ter nonsense NM_001322968.2:c.1192C>T NP_001309897.1:p.Arg398Ter nonsense NM_001322969.2:c.1192C>T NP_001309898.1:p.Arg398Ter nonsense NM_001322970.2:c.1192C>T NP_001309899.1:p.Arg398Ter nonsense NM_001322971.2:c.871C>T NP_001309900.1:p.Arg291Ter nonsense NM_001322974.2:c.592C>T NP_001309903.1:p.Arg198Ter nonsense NC_000010.11:g.124398070G>A NC_000010.10:g.126086639G>A NG_008861.1:g.25881C>T LRG_685:g.25881C>T LRG_685t1:c.1192C>T LRG_685p1:p.Arg398Ter - Protein change
- R398*, R291*, R198*, R260*
- Other names
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- Canonical SPDI
- NC_000010.11:124398069:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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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.
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0.00020 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00001
The Genome Aggregation Database (gnomAD), exomes 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
Trans-Omics for Precision Medicine (TOPMed) 0.00002
1000 Genomes Project 0.00020
1000 Genomes Project 30x 0.00031
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 | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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. |
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OAT | - | - |
GRCh38 GRCh37 |
588 | 701 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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. |
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Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Mar 17, 2024 | RCV000542545.19 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 28, 2022 | RCV002298643.8 |
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. |
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Pathogenic
(Sep 28, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hyperornithinemia
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV002598603.1
First in ClinVar: Nov 05, 2022 Last updated: Nov 05, 2022 |
Comment:
Variant summary: OAT c.1192C>T (p.Arg398X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein. … (more)
Variant summary: OAT c.1192C>T (p.Arg398X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein. Truncations downstream of this position have been classified as pathogenic in ClinVar and is associated with Gyrate atrophy in HGMD. The variant allele was found at a frequency of 8e-06 in 250954 control chromosomes (gnomAD). c.1192C>T has been reported in the literature in individuals affected with Ornithine Aminotransferase Deficiency (examples: Michaud_1995 and Cleary_2005). These data indicate that the variant is associated with disease. Multiple publications have provided experimental evidence that this variant abolishes the protein function (example: Doimo_2012 and Cleary_2005). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
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Pathogenic
(Oct 01, 2022)
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criteria provided, single submitter
Method: clinical testing
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Ornithine aminotransferase deficiency
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000626795.3
First in ClinVar: Dec 26, 2017 Last updated: Feb 07, 2023 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg398*) 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.Arg398*) in the OAT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acid(s) of the OAT protein. This variant is present in population databases (rs200068769, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with gyrate atrophy of the choroid and the retina (PMID: 7887415). ClinVar contains an entry for this variant (Variation ID: 456519). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects OAT function (PMID: 7887415, 23076989). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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Ornithine aminotransferase deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV004048294.1
First in ClinVar: Oct 28, 2023 Last updated: Oct 28, 2023 |
Comment:
The stop gained variant c.1192C>T (p.Arg398Ter) in OAT gene has been reported in an individual affected with gyrate atrophy of the choroid and the retina … (more)
The stop gained variant c.1192C>T (p.Arg398Ter) in OAT gene has been reported in an individual affected with gyrate atrophy of the choroid and the retina (Michaud J et.al.,1995). Experimental studies have shown that this nonsense change leads to a drastic reduction of the OAT enzymatic activity (Doimo M et.al.,2013). This variant has been reported to the ClinVar database as Pathogenic. The p.Arg398Ter variant is novel (not in any individuals) in 1000 Genomes and allele frequency of 0.000797% is reported in gnomAD. The nucleotide change in OAT is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic (less)
Clinical Features:
Hyperornithinemia (present)
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Pathogenic
(Mar 17, 2024)
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criteria provided, single submitter
Method: clinical testing
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Ornithine aminotransferase deficiency
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004192205.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
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Pathogenic
(Aug 18, 2020)
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no assertion criteria provided
Method: clinical testing
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Gyrate atrophy
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002093801.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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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 |
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Functional analysis of missense mutations of OAT, causing gyrate atrophy of choroid and retina. | Doimo M | Human mutation | 2013 | PMID: 23076989 |
Ornithine aminotransferase deficiency: diagnostic difficulties in neonatal presentation. | Cleary MA | Journal of inherited metabolic disease | 2005 | PMID: 16151897 |
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 |
Text-mined citations for rs200068769 ...
HelpRecord last updated Oct 13, 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.