This variant, c.254_256del, results in the deletion of 1 amino acid(s) of the ACAT1 protein (p.Glu85del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individuals with beta-ketothiolase deficiency (PMID: 7749408, 27928777). This variant is also known as c.253_255del, c.248_250del. ClinVar contains an entry for this variant (Variation ID: 666470). 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 variant affects ACAT1 function (PMID: 7749408). 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.
ClinVar Genomic variation as it relates to human health
NM_000019.4(ACAT1):c.248AAG[2] (p.Glu85del)
Germline
Classification
Help
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.
(4)
Help
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.
Conflicting classifications of pathogenicity
Likely pathogenic(3); Uncertain significance(1)
Likely pathogenic(3); Uncertain significance(1)
4
criteria provided, conflicting classifications
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000019.4(ACAT1):c.248AAG[2] (p.Glu85del)
Variation ID: 666470 Accession: VCV000666470.9
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 11q22.3 11: 108134230-108134232 (GRCh38) [ NCBI UCSC ] 11: 108004957-108004959 (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 Aug 31, 2019 Jun 17, 2024 Mar 14, 2024 - HGVS
- ... more HGVS ... less HGVS
- Protein change
- E85del
- Other names
- -
- Canonical SPDI
- NC_000011.10:108134229:AAGAAGAAG:AAGAAG
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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
Help
The frequency of the allele represented by this VCV record.
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- Links
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. |
|||
| ACAT1 | - | - |
GRCh38 GRCh37 |
734 | 759 | |
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. |
|---|---|---|---|---|
| Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
|
Mar 14, 2024 | RCV000844775.12 |
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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|---|---|---|---|---|---|
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Likely pathogenic
(May 05, 2019)
|
criteria provided, single submitter
Method: research
|
Deficiency of acetyl-CoA acetyltransferase
Affected status: yes
Allele origin:
germline
|
Department of Pediatrics, Gifu University
Accession: SCV000966042.1
First in ClinVar: Aug 31, 2019 Last updated: Aug 31, 2019 |
Observation 1:
Number of individuals with the variant: 2
Clinical Features:
Ketoacidosis (present)
Family history: yes
Observation 2:
Method: Transient expression analysis of mutant cDNA
Result:
No detected mitochondrial acetoacetyl-CoA thiolase enzyme activity or protein
|
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Uncertain significance
(Feb 18, 2022)
|
criteria provided, single submitter
Method: clinical testing
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Deficiency of acetyl-CoA acetyltransferase
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001222316.2
First in ClinVar: Apr 15, 2020 Last updated: Feb 07, 2023 |
Comment:
This variant, c.254_256del, results in the deletion of 1 amino acid(s) of the ACAT1 protein (p.Glu85del), but otherwise preserves the integrity of the reading frame. … (more)
This variant, c.254_256del, results in the deletion of 1 amino acid(s) of the ACAT1 protein (p.Glu85del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individuals with beta-ketothiolase deficiency (PMID: 7749408, 27928777). This variant is also known as c.253_255del, c.248_250del. ClinVar contains an entry for this variant (Variation ID: 666470). 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 variant affects ACAT1 function (PMID: 7749408). 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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Likely pathogenic
(Dec 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of acetyl-CoA acetyltransferase
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV002021276.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
|
|
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Likely pathogenic
(Mar 14, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Deficiency of acetyl-CoA acetyltransferase
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004214611.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
Comment:
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. |
Comment:
This variant, c.254_256del, results in the deletion of 1 amino acid(s) of the ACAT1 protein (p.Glu85del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has been observed in individuals with beta-ketothiolase deficiency (PMID: 7749408, 27928777). This variant is also known as c.253_255del, c.248_250del. ClinVar contains an entry for this variant (Variation ID: 666470). 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 variant affects ACAT1 function (PMID: 7749408). 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.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mutation update on ACAT1 variants associated with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency. | Abdelkreem E | Human mutation | 2019 | PMID: 31268215 |
| Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency. | Abdelkreem E | JIMD reports | 2017 | PMID: 27928777 |
| Characterization of six mutations in five Spanish patients with mitochondrial acetoacetyl-CoA thiolase deficiency: effects of amino acid substitutions on tertiary structure. | Fukao T | Molecular genetics and metabolism | 2002 | PMID: 11914035 |
| Molecular basis of beta-ketothiolase deficiency: mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene. | Fukao T | Human mutation | 1995 | PMID: 7749408 |
Text-mined citations for rs866364527 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 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.