NM_000019.4(ACAT1):c.1136G>T (p.Gly379Val) AND Deficiency of acetyl-CoA acetyltransferase

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: May 26, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:

Allele description [Variation Report for NM_000019.4(ACAT1):c.1136G>T (p.Gly379Val)]

NM_000019.4(ACAT1):c.1136G>T (p.Gly379Val)

ACAT1:acetyl-CoA acetyltransferase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000019.4(ACAT1):c.1136G>T (p.Gly379Val)
  • NC_000011.10:g.108146332G>T
  • NG_009888.1:g.29802G>T
  • NG_009888.2:g.34628G>T
  • NM_000019.4:c.1136G>TMANE SELECT
  • NP_000010.1:p.Gly379Val
  • LRG_1400t1:c.1136G>T
  • LRG_1400:g.34628G>T
  • LRG_1400p1:p.Gly379Val
  • NC_000011.9:g.108017059G>T
  • NM_000019.3:c.1136G>T
  • P24752:p.Gly379Val
Protein change:
G379V; GLY379VAL
UniProtKB: P24752#VAR_007506; OMIM: 607809.0008; dbSNP: rs120074143
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000019.4:c.1136G>T - 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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000023131OMIMno assertion criteria providedPathogenic
(Mar 1, 1994)
germlineliterature only

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

SCV000966118Department of Pediatrics, Gifu Universitycriteria provided, single submitter
Likely pathogenic
(May 5, 2019)

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

SCV001486268Invitaecriteria provided, single submitter
Uncertain significance
(May 26, 2020)
germlineclinical testing

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
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Mutations which alter splicing in the human hypoxanthine-guanine phosphoribosyltransferase gene.

Steingrimsdottir H, Rowley G, Dorado G, Cole J, Lehmann AR.

Nucleic Acids Res. 1992 Mar 25;20(6):1201-8.

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 (6)

Details of each submission

From OMIM, SCV000023131.1

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


Fukao et al. (1994) reported a Caucasian girl, born to nonconsanguineous parents, in whom the diagnosis of 3-ketothiolase deficiency (203750) was made when she was 3 years old and after multiple ketoacidotic attacks. Her growth and development were normal, and there was no mental retardation. She was found to be a compound heterozygote; the maternal allele had a 1136G-to-T transversion, resulting in a gly379-to-val substitution (G379V) in the thiolase precursor. Cells transfected with cDNA carrying the G379V mutation showed no evidence of restored T2 activity. The paternal allele was associated with exon 8 skipping at the cDNA level. In the paternal allele at the gene level, a C-to-T transition causing a gln272-to-ter (Q272X) change was identified within exon 8, 13 bp from the 5-prime splice site of intron 8. Splicing experiments showed that the exonic mutation caused partial skipping of exon 8. This substitution was thought to alter the secondary structure of T2 pre-mRNA around exon 8 and thus impede normal splicing. They cited a similar situation reported by Steingrimsdottir et al. (1992), who detected aberrant splicing in the HGPRT (308000) gene resulting from a mutation located 13 nucleotides from the 5-prime splice site of intron 8 and causing exon 8 skipping in 90% of HGPRT transcripts.

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

From Department of Pediatrics, Gifu University, SCV000966118.1

#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

From Invitae, SCV001486268.1

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


This sequence change replaces glycine with valine at codon 379 of the ACAT1 protein (p.Gly379Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 7907600). 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: 2839). This variant has been reported to affect ACAT1 protein 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.

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

Last Updated: Mar 12, 2021

Support Center