NM_000019.4(ACAT1):c.1163+2T>C AND Deficiency of acetyl-CoA acetyltransferase

Germline classification:: 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:: RCV000002971.3

Allele description [Variation Report for NM_000019.4(ACAT1):c.1163+2T>C]

NM_000019.4(ACAT1):c.1163+2T>C

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.1163+2T>C

HGVS:

NC_000011.10:g.108146361T>C
NG_009888.2:g.34657T>C
NM_000019.4:c.1163+2T>CMANE SELECT
NM_001386677.1:c.1163+2T>C
NM_001386678.1:c.848+2T>C
NM_001386679.1:c.866+2T>C
NM_001386681.1:c.893+2T>C
NM_001386682.1:c.893+2T>C
NM_001386685.1:c.893+2T>C
NM_001386686.1:c.893+2T>C
NM_001386687.1:c.893+2T>C
NM_001386688.1:c.893+2T>C
NM_001386689.1:c.893+2T>C
NM_001386690.1:c.893+2T>C
NM_001386691.1:c.893+2T>C
LRG_1400t1:c.1163+2T>C
LRG_1400:g.34657T>C
NC_000011.9:g.108017088T>C
NG_009888.1:g.29831T>C
NM_000019.3:c.1163+2T>C

Nucleotide change:

IVS11, T-C, +2

Links:

OMIM: 607809.0006; dbSNP: rs1280110907

NCBI 1000 Genomes Browser:

rs1280110907

Molecular consequence:

NM_000019.4:c.1163+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386677.1:c.1163+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386678.1:c.848+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386679.1:c.866+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386681.1:c.893+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386682.1:c.893+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386685.1:c.893+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386686.1:c.893+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386687.1:c.893+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386688.1:c.893+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386689.1:c.893+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386690.1:c.893+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001386691.1:c.893+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

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
SCV000023129	OMIM	no assertion criteria provided	Pathogenic (Jan 1, 1993)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 4690360, 8103405
SCV000966122	Department of Pediatrics, Gifu University	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 5, 2019)	germline	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 31268215

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000023129

OMIM

no assertion criteria provided

Pathogenic
(Jan 1, 1993)

germline

literature only

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

SCV000966122

Department of Pediatrics, Gifu University

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 5, 2019)

germline

research

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	yes	4	4	not provided	not provided	yes	research

Citations

PubMed

An inherited disorder of isoleucine catabolism causing accumulation of alpha-methylacetoacetate and alpha-methyl-beta -hydroxybutyrate, and intermittent metabolic acidosis.

Daum RS, Scriver CR, Mamer OA, Delvin E, Lamm P, Goldman H.

Pediatr Res. 1973 Mar;7(3):149-60. No abstract available.

PubMed [citation]

PMID:: 4690360

Molecular studies of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in the two original families.

Fukao T, Yamaguchi S, Scriver CR, Dunbar G, Wakazono A, Kano M, Orii T, Hashimoto T.

Hum Mutat. 1993;2(3):214-20.

PubMed [citation]

PMID:: 8103405

See all PubMed Citations (4)

Details of each submission

From OMIM, SCV000023129.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In a patient from the Dutch family in which 3-ketothiolase deficiency (203750) was first described by Daum et al. (1973), Fukao et al. (1993) demonstrated homozygosity for a 4-bp insertion (GCAG), a derived mutation. The primary mutation was an AG/gt to AG/gc transition at the 5-prime splice-junction site in intron 11. An alternative splice site 4 bp downstream was used, which caused a frameshift and replaced 39 C-terminal residues by 70 nonfunctional residues. Fukao et al. (1993) provided a 20-year follow-up on the proband in this family and on the 2 affected sibs in the Chilean family (see 607809.0007) reported by Daum et al. (1973). All had developed normally, had had no recurrence of acute metabolic decompensation since 1973 despite persistent abnormal organic aciduria (2-methyl-3-hydroxybutyrate, 2-methylacetoacetate), and were gainfully employed adults. They completed high school and 1 had attended university.

#	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, SCV000966122.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	yes	research	PubMed (2)

#	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		4	not provided	4	not provided

Last Updated: Mar 30, 2024

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