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NM_000019.4(ACAT1):c.1199A>G (p.His400Arg) AND Deficiency of acetyl-CoA acetyltransferase

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Sep 2, 2021
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:
RCV000505498.11

Allele description [Variation Report for NM_000019.4(ACAT1):c.1199A>G (p.His400Arg)]

NM_000019.4(ACAT1):c.1199A>G (p.His400Arg)

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.1199A>G (p.His400Arg)
HGVS:
  • NC_000011.10:g.108147305A>G
  • NG_009888.2:g.35601A>G
  • NM_000019.4:c.1199A>GMANE SELECT
  • NP_000010.1:p.His400Arg
  • LRG_1400t1:c.1199A>G
  • LRG_1400:g.35601A>G
  • LRG_1400p1:p.His400Arg
  • NC_000011.9:g.108018032A>G
  • NG_009888.1:g.30775A>G
  • NM_000019.3:c.1199A>G
Protein change:
H400R
Links:
dbSNP: rs761086326
NCBI 1000 Genomes Browser:
rs761086326
Molecular consequence:
  • NM_000019.4:c.1199A>G - 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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000599597Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
no assertion criteria provided
Likely pathogenic
(Sep 11, 2017) 		germlineclinical testing

SCV000940586Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 2, 2021) 		germlineclinical testing

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

SCV002090077Natera, Inc.
no assertion criteria provided
Uncertain significance
(Jan 27, 2021) 		germlineclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
Hindu/Gujaratigermlineyes1not providednot providednot providednot providedclinical testing

Citations

PubMed

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

Details of each submission

From Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics, SCV000599597.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Hindu/Gujarati1not providednot providedclinical testingnot provided

Description

The variant c.1199A>G(p.H400R) is not reported in 1000 genomes database and has minor allele frequency of 0.0016% in ExAC database. The in silico prediction of this variant is damaging by LRT, PolyPhen, SIFT and MutationTaster.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000940586.5

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

Description

This sequence change replaces histidine with arginine at codon 400 of the ACAT1 protein (p.His400Arg). The histidine residue is highly conserved and there is a small physicochemical difference between histidine and arginine. This variant is present in population databases (rs761086326, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with ACAT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 438580). 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: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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

From Natera, Inc., SCV002090077.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024