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NM_000019.4(ACAT1):c.375_376del (p.Ala127fs) AND Deficiency of acetyl-CoA acetyltransferase

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 14, 2023
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:
RCV002781120.2

Allele description [Variation Report for NM_000019.4(ACAT1):c.375_376del (p.Ala127fs)]

NM_000019.4(ACAT1):c.375_376del (p.Ala127fs)

Gene:
ACAT1:acetyl-CoA acetyltransferase 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11q22.3
Genomic location:
Preferred name:
NM_000019.4(ACAT1):c.375_376del (p.Ala127fs)
HGVS:
  • NC_000011.10:g.108135182_108135183del
  • NG_009888.2:g.23478_23479del
  • NM_000019.4:c.375_376delMANE SELECT
  • NM_001386677.1:c.375_376del
  • NM_001386678.1:c.120+3228_120+3229del
  • NM_001386679.1:c.78_79del
  • NM_001386681.1:c.105_106del
  • NM_001386682.1:c.105_106del
  • NM_001386685.1:c.105_106del
  • NM_001386686.1:c.105_106del
  • NM_001386687.1:c.105_106del
  • NM_001386688.1:c.105_106del
  • NM_001386689.1:c.105_106del
  • NM_001386690.1:c.105_106del
  • NM_001386691.1:c.105_106del
  • NP_000010.1:p.Ala127fs
  • NP_001373606.1:p.Ala127fs
  • NP_001373608.1:p.Ala28fs
  • NP_001373610.1:p.Ala37fs
  • NP_001373611.1:p.Ala37fs
  • NP_001373614.1:p.Ala37fs
  • NP_001373615.1:p.Ala37fs
  • NP_001373616.1:p.Ala37fs
  • NP_001373617.1:p.Ala37fs
  • NP_001373618.1:p.Ala37fs
  • NP_001373619.1:p.Ala37fs
  • NP_001373620.1:p.Ala37fs
  • LRG_1400t1:c.375_376del
  • LRG_1400:g.23478_23479del
  • LRG_1400p1:p.Ala127fs
  • NC_000011.9:g.108005908_108005909del
  • NC_000011.9:g.108005909_108005910del
  • NR_170162.1:n.415_416del
Protein change:
A127fs
Molecular consequence:
  • NM_000019.4:c.375_376del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386677.1:c.375_376del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386679.1:c.78_79del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386681.1:c.105_106del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386682.1:c.105_106del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386685.1:c.105_106del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386686.1:c.105_106del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386687.1:c.105_106del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386688.1:c.105_106del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386689.1:c.105_106del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386690.1:c.105_106del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386691.1:c.105_106del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001386678.1:c.120+3228_120+3229del - intron variant - [Sequence Ontology: SO:0001627]
  • NR_170162.1:n.415_416del - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003031052Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Aug 14, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV003031052.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1988079). This variant has not been reported in the literature in individuals affected with ACAT1-related conditions. This variant is present in population databases (rs774418317, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Ala127Phefs*49) 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).

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

Last Updated: Mar 30, 2024