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

Clinical significance:Uncertain significance (Last evaluated: Mar 19, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

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

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

ACAT1:acetyl-CoA acetyltransferase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000019.4(ACAT1):c.1199A>G (p.His400Arg)
  • NC_000011.10:g.108147305A>G
  • NG_009888.1:g.30775A>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
  • NM_000019.3:c.1199A>G
Protein change:
dbSNP: rs761086326
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000019.4:c.1199A>G - missense variant - [Sequence Ontology: SO:0001583]


Deficiency of acetyl-CoA acetyltransferase
Alpha-methylacetoaceticaciduria; 2-methyl-3-hydroxybutyricacidemia; Mitochondrial acetoacetyl-CoA Thiolase deficiency; See all synonyms [MedGen]
MONDO: MONDO:0008760; MedGen: C1536500; Orphanet: 134; OMIM: 203750

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000599597Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Geneticsno assertion criteria providedLikely pathogenic
(Sep 11, 2017)
germlineclinical testing

SCV000940586Invitaecriteria provided, single submitter
Uncertain significance
(Mar 19, 2019)
germlineclinical testing

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

Summary from all submissions

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



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]

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


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.

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

From Invitae, SCV000940586.3

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


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 with ACAT1-related disease. 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.

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

Last Updated: Mar 14, 2021

Support Center