ClinVar Miner

Submissions for variant NM_000019.4(ACAT1):c.455G>C (p.Gly152Ala)

gnomAD frequency: 0.00006  dbSNP: rs762991875
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000179236 SCV000231452 likely pathogenic not provided 2015-02-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000779680 SCV000916408 pathogenic Deficiency of acetyl-CoA acetyltransferase 2017-09-28 criteria provided, single submitter clinical testing Variant summary: The ACAT1 c.455G>C (p.Gly152Ala) variant involves the alteration of a conserved nucleotide located in the buried Nbeta4 near an active site (Fukao_2002) and 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). Functional studies support these predictions observing the variant to affect protein folding and/or dimerization but also accumulated unstable mutant protein (Fukao_2002 and Zhang_2004). This variant was found in 14/246162 control chromosomes at a frequency of 0.0000569, which does not exceed the estimated maximal expected allele frequency of a pathogenic ACAT1 variant (0.0028868). Multiple publications cite the variant in affected compound heterozygote patients. In addition, a clinical diagnostic laboratory classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Department of Pediatrics, Gifu University RCV000779680 SCV000966059 likely pathogenic Deficiency of acetyl-CoA acetyltransferase 2019-05-05 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV000779680 SCV002242091 pathogenic Deficiency of acetyl-CoA acetyltransferase 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 152 of the ACAT1 protein (p.Gly152Ala). This variant is present in population databases (rs762991875, gnomAD 0.03%). This missense change has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 7749408, 15128923, 28255778). ClinVar contains an entry for this variant (Variation ID: 198029). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACAT1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ACAT1 function (PMID: 7749408, 15128923). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000779680 SCV002812842 pathogenic Deficiency of acetyl-CoA acetyltransferase 2022-03-08 criteria provided, single submitter clinical testing
Baylor Genetics RCV000779680 SCV004212861 pathogenic Deficiency of acetyl-CoA acetyltransferase 2024-03-19 criteria provided, single submitter clinical testing

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