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

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: May 5, 2019
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:: RCV000002966.3

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

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

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.1138G>A (p.Ala380Thr)

Other names:

A347T

HGVS:

NC_000011.10:g.108146334G>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
NG_009888.1:g.29804G>A
NM_000019.3:c.1138G>A
P24752:p.Ala380Thr

Protein change:

A380T; ALA347THR

Links:

UniProtKB: P24752#VAR_007507; OMIM: 607809.0001; dbSNP: rs120074140

NCBI 1000 Genomes Browser:

rs120074140

Molecular consequence:

NM_000019.4:c.1138G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000023124	OMIM	no assertion criteria provided	Pathogenic (Aug 30, 1991)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000966119	Department of Pediatrics, Gifu University	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (May 5, 2019)	germline	research	PubMed (3) [See all records that cite these PMIDs] 25741868, 11161836, 31268215

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000023124

OMIM

no assertion criteria provided

Pathogenic
(Aug 30, 1991)

germline

literature only

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

SCV000966119

Department of Pediatrics, Gifu University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(May 5, 2019)

germline

research

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	1	not provided	not provided	yes	research
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

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]

PMID:: 1715688

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]

PMID:: 25741868
PMCID:: PMC4544753

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000023124.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department of Pediatrics, Gifu University, SCV000966119.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	yes	research	PubMed (3)
2	not provided	not provided	not provided	not provided	research	PubMed (3)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	1	not provided
2	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Mar 30, 2024

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