ClinVar Genomic variation as it relates to human health
NM_000274.4(OAT):c.1276C>T (p.Arg426Ter)
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.1276C>T (p.Arg426Ter)
Variation ID: 177 Accession: VCV000000177.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q26.13 10: 124397986 (GRCh38) [ NCBI UCSC ] 10: 126086555 (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 Apr 4, 2013 Feb 14, 2024 Oct 18, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000274.4:c.1276C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000265.1:p.Arg426Ter nonsense NM_001171814.2:c.862C>T NP_001165285.1:p.Arg288Ter nonsense NM_001322965.2:c.1276C>T NP_001309894.1:p.Arg426Ter nonsense NM_001322966.2:c.1276C>T NP_001309895.1:p.Arg426Ter nonsense NM_001322967.2:c.1276C>T NP_001309896.1:p.Arg426Ter nonsense NM_001322968.2:c.1276C>T NP_001309897.1:p.Arg426Ter nonsense NM_001322969.2:c.1276C>T NP_001309898.1:p.Arg426Ter nonsense NM_001322970.2:c.1276C>T NP_001309899.1:p.Arg426Ter nonsense NM_001322971.2:c.955C>T NP_001309900.1:p.Arg319Ter nonsense NM_001322974.2:c.676C>T NP_001309903.1:p.Arg226Ter nonsense NC_000010.11:g.124397986G>A NC_000010.10:g.126086555G>A NG_008861.1:g.25965C>T LRG_685:g.25965C>T LRG_685t1:c.1276C>T LRG_685p1:p.Arg426Ter - Protein change
- R426*, R288*, R226*, R319*
- Other names
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- Canonical SPDI
- NC_000010.11:124397985: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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Allele frequency
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The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00000
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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 |
579 | 690 |
Conditions - Germline
Condition
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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
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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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 (5) |
criteria provided, multiple submitters, no conflicts
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Oct 18, 2023 | RCV000000200.19 | |
Pathogenic (1) |
criteria provided, single submitter
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Jun 14, 2022 | RCV002271362.8 |
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
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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
(Jun 14, 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: SCV002555863.1
First in ClinVar: Aug 08, 2022 Last updated: Aug 08, 2022 |
Comment:
Variant summary: OAT c.1276C>T (p.Arg426X) results in a premature termination codon in the last exon of the protein, predicted to cause a truncation of the … (more)
Variant summary: OAT c.1276C>T (p.Arg426X) results in a premature termination codon in the last exon of the protein, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 250712 control chromosomes (gnomAD). c.1276C>T has been reported in the literature in homozygous and compound heterozygous individuals affected with Ornithine Aminotransferase Deficiency (examples: Katagiri_2014 and Mashima_1994). These data indicate that the variant is very likely to be associated with disease. In yeast this variant effect results in <10% of normal activity (Doimo_2012). 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
(Aug 29, 2023)
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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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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV004030477.1
First in ClinVar: Sep 03, 2023 Last updated: Sep 03, 2023 |
Clinical Features:
Cataract (present) , Blindness (present) , Chorioretinal dystrophy (present)
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Pathogenic
(Oct 18, 2023)
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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: SCV004192206.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Aug 29, 2023)
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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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Invitae
Accession: SCV001211238.5
First in ClinVar: Apr 15, 2020 Last updated: Feb 14, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Arg426*) in the OAT gene. While … (more)
For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Arg426*) in the OAT gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 14 amino acid(s) of the OAT protein. This variant is present in population databases (rs121965058, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with gyrate atrophy (PMID: 1609808, 24429551). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 177). 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: 23076989). (less)
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Pathogenic
(Jul 01, 1992)
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no assertion criteria provided
Method: literature only
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GYRATE ATROPHY OF CHOROID AND RETINA
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000020343.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
See 613349.0032 and Mashima et al. (1992); the R426X mutation resulted from a homozygous C-to-T transition in exon 11.
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Pathogenic
(Apr 09, 2021)
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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: SCV002088028.1
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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OAT mutations and clinical features in two Japanese brothers with gyrate atrophy of the choroid and retina. | Katagiri S | Documenta ophthalmologica. Advances in ophthalmology | 2014 | PMID: 24429551 |
Functional analysis of missense mutations of OAT, causing gyrate atrophy of choroid and retina. | Doimo M | Human mutation | 2013 | PMID: 23076989 |
Rapid and efficient molecular analysis of gyrate atrophy using denaturing gradient gel electrophoresis. | Mashima Y | Investigative ophthalmology & visual science | 1994 | PMID: 8125717 |
Nonsense-codon mutations of the ornithine aminotransferase gene with decreased levels of mutant mRNA in gyrate atrophy. | Mashima Y | American journal of human genetics | 1992 | PMID: 1609808 |
Text-mined citations for rs121965058 ...
HelpRecord last updated Apr 20, 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.