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NM_000019.4(ACAT1):c.902C>T (p.Ala301Val) AND Deficiency of acetyl-CoA acetyltransferase

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 27, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001915365.5

Allele description [Variation Report for NM_000019.4(ACAT1):c.902C>T (p.Ala301Val)]

NM_000019.4(ACAT1):c.902C>T (p.Ala301Val)

Gene:
ACAT1:acetyl-CoA acetyltransferase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000019.4(ACAT1):c.902C>T (p.Ala301Val)
HGVS:
  • NC_000011.10:g.108142512C>T
  • NG_009888.2:g.30808C>T
  • NM_000019.4:c.902C>TMANE SELECT
  • NM_001386677.1:c.902C>T
  • NM_001386678.1:c.587C>T
  • NM_001386679.1:c.605C>T
  • NM_001386681.1:c.632C>T
  • NM_001386682.1:c.632C>T
  • NM_001386685.1:c.632C>T
  • NM_001386686.1:c.632C>T
  • NM_001386687.1:c.632C>T
  • NM_001386688.1:c.632C>T
  • NM_001386689.1:c.632C>T
  • NM_001386690.1:c.632C>T
  • NM_001386691.1:c.632C>T
  • NP_000010.1:p.Ala301Val
  • NP_001373606.1:p.Ala301Val
  • NP_001373607.1:p.Ala196Val
  • NP_001373608.1:p.Ala202Val
  • NP_001373610.1:p.Ala211Val
  • NP_001373611.1:p.Ala211Val
  • NP_001373614.1:p.Ala211Val
  • NP_001373615.1:p.Ala211Val
  • NP_001373616.1:p.Ala211Val
  • NP_001373617.1:p.Ala211Val
  • NP_001373618.1:p.Ala211Val
  • NP_001373619.1:p.Ala211Val
  • NP_001373620.1:p.Ala211Val
  • LRG_1400t1:c.902C>T
  • LRG_1400:g.30808C>T
  • LRG_1400p1:p.Ala301Val
  • NC_000011.9:g.108013239C>T
  • NR_170162.1:n.942C>T
  • NR_170163.1:n.935C>T
Protein change:
A196V
Links:
dbSNP: rs747860630
NCBI 1000 Genomes Browser:
rs747860630
Molecular consequence:
  • NM_000019.4:c.902C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386677.1:c.902C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386678.1:c.587C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386679.1:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386681.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386682.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386685.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386686.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386687.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386688.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386689.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386690.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386691.1:c.632C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_170162.1:n.942C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_170163.1:n.935C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Deficiency of acetyl-CoA acetyltransferase
Synonyms:
3-KETOTHIOLASE DEFICIENCY; 3-OXOTHIOLASE DEFICIENCY; MITOCHONDRIAL ACETOACETYL-CoA THIOLASE DEFICIENCY; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0008760; MedGen: C1536500; Orphanet: 134; OMIM: 203750

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002171712Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Mar 27, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular, biochemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients.

Wakazono A, Fukao T, Yamaguchi S, Hori T, Orii T, Lambert M, Mitchell GA, Lee GW, Hashimoto T.

Hum Mutat. 1995;5(1):34-42.

PubMed [citation]
PMID:
7728148

Molecular basis of beta-ketothiolase deficiency: mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene.

Fukao T, Yamaguchi S, Orii T, Hashimoto T.

Hum Mutat. 1995;5(2):113-20. Review.

PubMed [citation]
PMID:
7749408
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002171712.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 301 of the ACAT1 protein (p.Ala301Val). This variant is present in population databases (rs747860630, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with ACAT1-related conditions. 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 ACAT1 protein function. This variant disrupts the p.Ala301 amino acid residue in ACAT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 7728148, 7749408). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jan 13, 2025