ClinVar Genomic variation as it relates to human health
NM_000030.3(AGXT):c.865C>T (p.Arg289Cys)
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_000030.3(AGXT):c.865C>T (p.Arg289Cys)
Variation ID: 204055 Accession: VCV000204055.11
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q37.3 2: 240877555 (GRCh38) [ NCBI UCSC ] 2: 241816972 (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 Jul 21, 2015 Mar 26, 2023 Feb 23, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000030.3:c.865C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000021.1:p.Arg289Cys missense NC_000002.12:g.240877555C>T NC_000002.11:g.241816972C>T NG_008005.1:g.13811C>T P21549:p.Arg289Cys - Protein change
- R289C
- Other names
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- Canonical SPDI
- NC_000002.12:240877554:C:T
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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.
Exome Aggregation Consortium (ExAC) 0.00073
Trans-Omics for Precision Medicine (TOPMed) 0.00037
The Genome Aggregation Database (gnomAD), exomes 0.00039
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00042
The Genome Aggregation Database (gnomAD) 0.00043
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
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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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AGXT | - | - |
GRCh38 GRCh37 |
907 | 1025 |
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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Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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May 10, 2022 | RCV000186261.17 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 23, 2023 | RCV003155111.8 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 7, 2020 | RCV002517832.9 |
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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Uncertain significance
(Aug 25, 2017)
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criteria provided, single submitter
Method: clinical testing
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Primary hyperoxaluria, type I
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000793612.1
First in ClinVar: Jul 21, 2015 Last updated: Jul 21, 2015 |
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Uncertain significance
(Apr 28, 2017)
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criteria provided, single submitter
Method: clinical testing
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Primary hyperoxaluria, type I
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001297136.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(May 10, 2022)
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criteria provided, single submitter
Method: clinical testing
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Primary hyperoxaluria, type I
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000895452.2
First in ClinVar: Mar 31, 2019 Last updated: Dec 31, 2022 |
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Uncertain significance
(Oct 07, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV003265766.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine with cysteine at codon 289 of the AGXT protein (p.Arg289Cys). The arginine residue is moderately conserved and there is a … (more)
This sequence change replaces arginine with cysteine at codon 289 of the AGXT protein (p.Arg289Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs180177290, ExAC 0.1%). This variant has been observed in individual(s) withprimary hyperoxaluria (PMID: 10541294). ClinVar contains an entry for this variant (Variation ID: 204055). Experimental studies have shown that this variant does not substantially affect AGXT protein function (PMID: 22923379). 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. (less)
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Uncertain significance
(Feb 23, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV003845133.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
Comment:
Variant summary: AGXT c.865C>T (p.Arg289Cys) results in a non-conservative amino acid change located in the Aminotransferase class V domain (IPR000192) of the encoded protein sequence. … (more)
Variant summary: AGXT c.865C>T (p.Arg289Cys) results in a non-conservative amino acid change located in the Aminotransferase class V domain (IPR000192) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00039 in 152912 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in AGXT causing Primary Hyperoxaluria Type 1 (0.00039 vs 0.0024), allowing no conclusion about variant significance. c.865C>T has been reported in the literature in individuals affected with Primary Hyperoxaluria Type 1 (example: Rinalt_1999 and Frishberg_2005). These report(s) do not provide unequivocal conclusions about association of the variant with Primary Hyperoxaluria Type 1. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (example: Pittman_2012). Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. (less)
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Uncertain significance
(Nov 27, 2014)
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no assertion criteria provided
Method: in vitro
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Primary hyperoxaluria, type I
Affected status: yes
Allele origin:
germline
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Clinical Biochemistry Laboratory, Health Services Laboratory
Accession: SCV000239585.1
First in ClinVar: Jul 21, 2015 Last updated: Jul 21, 2015 |
Result:
No affect on activity or stability (C Tucker, personal communication 20/9/12).
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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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Rapid profiling of disease alleles using a tunable reporter of protein misfolding. | Pittman AM | Genetics | 2012 | PMID: 22923379 |
Intra-familial clinical heterogeneity: absence of genotype-phenotype correlation in primary hyperoxaluria type 1 in Israel. | Frishberg Y | American journal of nephrology | 2005 | PMID: 15961946 |
Primary hyperoxaluria type I: a model for multiple mutations in a monogenic disease within a distinct ethnic group. | Rinat C | Journal of the American Society of Nephrology : JASN | 1999 | PMID: 10541294 |
http://www.uclh.nhs.uk/OurServices/ServiceA-Z/PATH/PATHBIOMED/CBIO/Documents/AGXT%20mutation%20database.pdf | - | - | - | - |
Text-mined citations for rs180177290 ...
HelpRecord last updated Oct 08, 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.