NM_000019.4(ACAT1):c.854C>T (p.Thr285Ile) AND Deficiency of acetyl-CoA acetyltransferase

Clinical significance:Uncertain significance (Last evaluated: Mar 4, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000844816.2

Allele description [Variation Report for NM_000019.4(ACAT1):c.854C>T (p.Thr285Ile)]

NM_000019.4(ACAT1):c.854C>T (p.Thr285Ile)

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.854C>T (p.Thr285Ile)
HGVS:
  • NC_000011.10:g.108142464C>T
  • NG_009888.1:g.25934C>T
  • NG_009888.2:g.30760C>T
  • NM_000019.4:c.854C>TMANE SELECT
  • NP_000010.1:p.Thr285Ile
  • LRG_1400t1:c.854C>T
  • LRG_1400:g.30760C>T
  • LRG_1400p1:p.Thr285Ile
  • NC_000011.9:g.108013191C>T
  • NM_000019.3:c.854C>T
Protein change:
T285I
Links:
dbSNP: rs1239221388
NCBI 1000 Genomes Browser:
rs1239221388
Molecular consequence:
  • NM_000019.4:c.854C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000966092Department of Pediatrics, Gifu Universitycriteria provided, single submitter
Uncertain significance
(May 5, 2019)
germlineliterature only

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

SCV001558583Invitaecriteria provided, single submitter
Uncertain significance
(Mar 4, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown11not providednot providednot providedclinical testing, literature only

Citations

PubMed

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

Mutation update on ACAT1 variants associated with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency.

Abdelkreem E, Harijan RK, Yamaguchi S, Wierenga RK, Fukao T.

Hum Mutat. 2019 Oct;40(10):1641-1663. doi: 10.1002/humu.23831. Epub 2019 Jul 3. Review.

PubMed [citation]
PMID:
31268215
PMCID:
PMC6790690
See all PubMed Citations (4)

Details of each submission

From Department of Pediatrics, Gifu University, SCV000966092.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedliterature only PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not provided1not provided

From Invitae, SCV001558583.1

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

Description

This sequence change replaces threonine with isoleucine at codon 285 of the ACAT1 protein (p.Thr285Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 24516753). ClinVar contains an entry for this variant (Variation ID: 666509). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Tolerated; PolyPhen-2: Probably Damaging; Align-GVGD: Class C1). 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. 5

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

Last Updated: Apr 18, 2021

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