NM_000019.4(ACAT1):c.1114C>T (p.Gln372Ter) AND Deficiency of acetyl-CoA acetyltransferase

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 8, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001936720.5

Allele description [Variation Report for NM_000019.4(ACAT1):c.1114C>T (p.Gln372Ter)]

NM_000019.4(ACAT1):c.1114C>T (p.Gln372Ter)

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.1114C>T (p.Gln372Ter)

HGVS:

NC_000011.10:g.108146310C>T
NG_009888.2:g.34606C>T
NM_000019.4:c.1114C>TMANE SELECT
NM_001386677.1:c.1114C>T
NM_001386678.1:c.799C>T
NM_001386679.1:c.817C>T
NM_001386681.1:c.844C>T
NM_001386682.1:c.844C>T
NM_001386685.1:c.844C>T
NM_001386686.1:c.844C>T
NM_001386687.1:c.844C>T
NM_001386688.1:c.844C>T
NM_001386689.1:c.844C>T
NM_001386690.1:c.844C>T
NM_001386691.1:c.844C>T
NP_000010.1:p.Gln372Ter
NP_001373606.1:p.Gln372Ter
NP_001373607.1:p.Gln267Ter
NP_001373608.1:p.Gln273Ter
NP_001373610.1:p.Gln282Ter
NP_001373611.1:p.Gln282Ter
NP_001373614.1:p.Gln282Ter
NP_001373615.1:p.Gln282Ter
NP_001373616.1:p.Gln282Ter
NP_001373617.1:p.Gln282Ter
NP_001373618.1:p.Gln282Ter
NP_001373619.1:p.Gln282Ter
NP_001373620.1:p.Gln282Ter
LRG_1400t1:c.1114C>T
LRG_1400:g.34606C>T
LRG_1400p1:p.Gln372Ter
NC_000011.9:g.108017037C>T
NR_170162.1:n.1089C>T
NR_170163.1:n.1147C>T

Protein change:

Q267*

Links:

dbSNP: rs2134791667

NCBI 1000 Genomes Browser:

rs2134791667

Molecular consequence:

NR_170162.1:n.1089C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_170163.1:n.1147C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000019.4:c.1114C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386677.1:c.1114C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386678.1:c.799C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386679.1:c.817C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386681.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386682.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386685.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386686.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386687.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386688.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386689.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386690.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001386691.1:c.844C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002225261	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 8, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 7749408, 28492532
SCV004214777	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Dec 21, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002225261

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 8, 2023)

germline

clinical testing

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

SCV004214777

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Dec 21, 2022)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular basis of beta-ketothiolase deficiency: mutations and polymorphisms in the human mitochondrial acetoacetyl-coenzyme A thiolase gene.

Fukao T, Yamaguchi S, Orii T, Hashimoto T.

Hum Mutat. 1995;5(2):113-20. Review.

PubMed [citation]

PMID:: 7749408

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002225261.3

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

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1439830). This variant has not been reported in the literature in individuals affected with ACAT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln372*) in the ACAT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACAT1 are known to be pathogenic (PMID: 7749408).

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

From Baylor Genetics, SCV004214777.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

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

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine