ClinVar Genomic variation as it relates to human health
NM_020686.6(ABAT):c.275G>A (p.Arg92Gln)
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_020686.6(ABAT):c.275G>A (p.Arg92Gln)
Variation ID: 162036 Accession: VCV000162036.5
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 16p13.2 16: 8750498 (GRCh38) [ NCBI UCSC ] 16: 8844355 (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 Jan 21, 2015 Feb 14, 2024 Dec 1, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_020686.6:c.275G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_065737.2:p.Arg92Gln missense NM_000663.5:c.275G>A NP_000654.2:p.Arg92Gln missense NM_001127448.2:c.275G>A NP_001120920.1:p.Arg92Gln missense NM_001386600.1:c.275G>A NP_001373529.1:p.Arg92Gln missense NM_001386601.1:c.275G>A NP_001373530.1:p.Arg92Gln missense NM_001386602.1:c.275G>A NP_001373531.1:p.Arg92Gln missense NM_001386603.1:c.275G>A NP_001373532.1:p.Arg92Gln missense NM_001386604.1:c.275G>A NP_001373533.1:p.Arg92Gln missense NM_001386605.1:c.275G>A NP_001373534.1:p.Arg92Gln missense NM_001386606.1:c.275G>A NP_001373535.1:p.Arg92Gln missense NM_001386607.1:c.275G>A NP_001373536.1:p.Arg92Gln missense NM_001386608.1:c.275G>A NP_001373537.1:p.Arg92Gln missense NM_001386609.1:c.275G>A NP_001373538.1:p.Arg92Gln missense NM_001386610.1:c.140G>A NP_001373539.1:p.Arg47Gln missense NM_001386611.1:c.140G>A NP_001373540.1:p.Arg47Gln missense NM_001386612.1:c.140G>A NP_001373541.1:p.Arg47Gln missense NM_001386613.1:c.140G>A NP_001373542.1:p.Arg47Gln missense NM_001386614.1:c.71-7259G>A intron variant NM_001386615.1:c.275G>A NP_001373544.1:p.Arg92Gln missense NM_001386616.1:c.275G>A NP_001373545.1:p.Arg92Gln missense NC_000016.10:g.8750498G>A NC_000016.9:g.8844355G>A NG_008432.1:g.80912G>A - Protein change
- R92Q, R47Q
- Other names
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- Canonical SPDI
- NC_000016.10:8750497: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.
Trans-Omics for Precision Medicine (TOPMed) 0.00000
The Genome Aggregation Database (gnomAD) 0.00001
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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ABAT | - | - |
GRCh38 GRCh37 |
716 | 805 |
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/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Dec 1, 2023 | RCV000149900.6 |
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
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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
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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
(Jan 01, 2014)
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criteria provided, single submitter
Method: research
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Gamma-aminobutyric acid transaminase deficiency
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Bonnen Lab, Baylor College of Medicine
Accession: SCV000148968.2
First in ClinVar: Jan 21, 2015 Last updated: Jan 21, 2015 |
Comment:
clinical and in vitro studies
Number of individuals with the variant: 1
Clinical Features:
severe psychomotor retardation (present) , intractable seizures (present) , hypotonia (present) , hyperreflexia (present) , elevated GABA in basal ganglia (present)
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Pathogenic
(Sep 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Gamma-aminobutyric acid transaminase deficiency
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004210702.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Likely pathogenic
(Dec 01, 2023)
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criteria provided, single submitter
Method: clinical testing
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Gamma-aminobutyric acid transaminase deficiency
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV004296386.1
First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 92 of the ABAT protein (p.Arg92Gln). … (more)
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 92 of the ABAT protein (p.Arg92Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with GABA transaminase deficiency (PMID: 20052547, 30617166). 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: 162036). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ABAT protein function with a negative predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. (less)
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Pathogenic
(Feb 01, 2010)
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no assertion criteria provided
Method: literature only
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GABA-TRANSAMINASE DEFICIENCY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000599468.2
First in ClinVar: Jan 21, 2015 Last updated: Oct 21, 2017 |
Comment on evidence:
In a 28-month-old Japanese female with GATA-transaminase deficiency (613163), Tsuji et al. (2010) identified compound heterozygous mutations in the ABAT gene: a c.275G-A transition (c.275G-A, … (more)
In a 28-month-old Japanese female with GATA-transaminase deficiency (613163), Tsuji et al. (2010) identified compound heterozygous mutations in the ABAT gene: a c.275G-A transition (c.275G-A, NM_000663.3), resulting in an arg92-to-gln (R92Q) substitution, and an exon deletion (c.199-?_316+?; 137150.0004). (less)
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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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Paroxysmal dyskinesias with drowsiness and thalamic lesions in GABA transaminase deficiency. | Morales-Briceño H | Neurology | 2019 | PMID: 30617166 |
The GABA transaminase, ABAT, is essential for mitochondrial nucleoside metabolism. | Besse A | Cell metabolism | 2015 | PMID: 25738457 |
A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy. | Tsuji M | Journal of inherited metabolic disease | 2010 | PMID: 20052547 |
Text-mined citations for rs724159992 ...
HelpRecord last updated May 01, 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.