NM_000019.4(ACAT1):c.1138G>A (p.Ala380Thr) AND Deficiency of acetyl-CoA acetyltransferase

Clinical significance:Likely pathogenic (Last evaluated: May 5, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000019.4(ACAT1):c.1138G>A (p.Ala380Thr)]

NM_000019.4(ACAT1):c.1138G>A (p.Ala380Thr)

ACAT1:acetyl-CoA acetyltransferase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000019.4(ACAT1):c.1138G>A (p.Ala380Thr)
  • NC_000011.10:g.108146334G>A
  • NG_009888.1:g.29804G>A
  • NG_009888.2:g.34630G>A
  • NM_000019.4:c.1138G>AMANE SELECT
  • NP_000010.1:p.Ala380Thr
  • LRG_1400t1:c.1138G>A
  • LRG_1400:g.34630G>A
  • LRG_1400p1:p.Ala380Thr
  • NC_000011.9:g.108017061G>A
  • NM_000019.3:c.1138G>A
  • P24752:p.Ala380Thr
Protein change:
A347T; ALA347THR
UniProtKB: P24752#VAR_007507; OMIM: 607809.0001; dbSNP: rs120074140
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000019.4:c.1138G>A - missense variant - [Sequence Ontology: SO:0001583]


Deficiency of acetyl-CoA acetyltransferase
Alpha-methylacetoaceticaciduria; 2-methyl-3-hydroxybutyricacidemia; Mitochondrial acetoacetyl-CoA Thiolase deficiency; See all synonyms [MedGen]
MONDO: MONDO:0008760; MedGen: C1536500; Orphanet: 134; OMIM: 203750

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000023124OMIMno assertion criteria providedPathogenic
(Aug 30, 1991)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV000966119Department of Pediatrics, Gifu Universitycriteria provided, single submitter
Likely pathogenic
(May 5, 2019)

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedgermlineyes11not providednot providedyesresearch



Evidence for a structural mutation (347Ala to Thr) in a German family with 3-ketothiolase deficiency.

Fukao T, Yamaguchi S, Tomatsu S, Orii T, Frauendienst-Egger G, Schrod L, Osumi T, Hashimoto T.

Biochem Biophys Res Commun. 1991 Aug 30;179(1):124-9.

PubMed [citation]

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000023124.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)


In a German boy with 3-ketothiolase deficiency (203750) born of nonconsanguineous parents, Fukao et al. (1991) found compound heterozygosity for 2 mutations in the ACAT1 gene: a G-to-A substitution, resulting in an ala347-to-thr substitution (A347T), inherited from the mother, and a mutation inherited from the father that abolished expression of the gene. Transfection analysis showed that the A347T substitution resulted in instability of the protein. The patient showed normal development until his first ketoacidotic attack at the age of 6 months, following which severe retardation developed. The diagnosis of 3-ketothiolase deficiency was made by urinary organic acid analysis during the attack.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Department of Pediatrics, Gifu University, SCV000966119.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providedyesresearch PubMed (3)
2not providednot providednot providednot providedresearch PubMed (3)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not provided1not provided
2germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 17, 2020

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