NM_000019.4(ACAT1):c.547G>A (p.Gly183Arg) AND Deficiency of acetyl-CoA acetyltransferase

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 29, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
3 submissions [Details]
Record status:

Allele description [Variation Report for NM_000019.4(ACAT1):c.547G>A (p.Gly183Arg)]

NM_000019.4(ACAT1):c.547G>A (p.Gly183Arg)

ACAT1:acetyl-CoA acetyltransferase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000019.4(ACAT1):c.547G>A (p.Gly183Arg)
Other names:
  • NC_000011.10:g.108139009G>A
  • NG_009888.1:g.22479G>A
  • NG_009888.2:g.27305G>A
  • NM_000019.4:c.547G>AMANE SELECT
  • NP_000010.1:p.Gly183Arg
  • LRG_1400t1:c.547G>A
  • LRG_1400:g.27305G>A
  • LRG_1400p1:p.Gly183Arg
  • NC_000011.9:g.108009736G>A
  • NM_000019.3:c.547G>A
  • P24752:p.Gly183Arg
Protein change:
G183R; GLY150ARG
UniProtKB: P24752#VAR_007501; OMIM: 607809.0002; dbSNP: rs120074141
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000019.4:c.547G>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)
SCV000023125OMIMno assertion criteria providedPathogenic
(Feb 1, 1992)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000966065Department of Pediatrics, Gifu Universitycriteria provided, single submitter
Likely pathogenic
(May 5, 2019)

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

SCV001582981Invitaecriteria provided, single submitter
(Mar 29, 2020)
germlineclinical testing

PubMed (4)
[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 providedgermlineyes53not providednot providedyesresearch
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Beta-ketothiolase deficiency in a family confirmed by in vitro enzymatic assays in fibroblasts.

Schutgens RB, Middleton B, vd Blij JF, Oorthuys JW, Veder HA, Vulsma T, Tegelaers WH.

Eur J Pediatr. 1982 Sep;139(1):39-42. No abstract available.

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 (8)

Details of each submission

From OMIM, SCV000023125.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)


Fukao et al. (1992) studied a Caucasian family reported by Schutgens et al. (1982). The family was unusual in that the father and a son had 3-ketothiolase deficiency (203750). Three mutant alleles of the ACAT1 gene were found. The father was a compound heterozygote: one allele had a 547G-A mutation, resulting in a gly150-to-arg (G150R) substitution, and the other allele had a GT-to-TT transition at the 5-prime splice site of intron 8, causing skipping of exon 8 in the cDNA (607809.0003). The son was also a compound heterozygote: one allele, inherited from his mother, had an AG-to-CG transition at the 3-prime splice site of intron 10, causing skipping of exon 11 of the cDNA (607809.0004), and the other allele derived from the father had the G150R substitution. Another son was an obligatory carrier of the mutant allele causing exon 8 skipping.

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

From Department of Pediatrics, Gifu University, SCV000966065.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided5not providedyesresearch PubMed (3)
2not providednot providednot providednot providedresearch PubMed (3)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided5not provided3not provided
2germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001582981.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)


This sequence change replaces glycine with arginine at codon 183 of the ACAT1 protein (p.Gly183Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs120074141, ExAC 0.01%). This variant has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 1346617, 28689740). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 2833). This variant has been reported to affect ACAT1 protein function (PMID: 7749408). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: May 14, 2021

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