ClinVar Miner

Submissions for variant NM_000019.4(ACAT1):c.578T>G (p.Met193Arg)

dbSNP: rs541517496
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pediatrics, Gifu University RCV000844795 SCV000966068 likely pathogenic Deficiency of acetyl-CoA acetyltransferase 2019-05-05 criteria provided, single submitter research
Invitae RCV000844795 SCV001217723 pathogenic Deficiency of acetyl-CoA acetyltransferase 2023-05-31 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ACAT1 function (PMID: 27928777). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 666490). This missense change has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 23958592, 27928777). This variant is present in population databases (rs541517496, gnomAD 0.01%). This sequence change replaces methionine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 193 of the ACAT1 protein (p.Met193Arg).
Revvity Omics, Revvity RCV000844795 SCV002021694 pathogenic Deficiency of acetyl-CoA acetyltransferase 2021-04-06 criteria provided, single submitter clinical testing
Lifecell International Pvt. Ltd RCV000844795 SCV003922041 pathogenic Deficiency of acetyl-CoA acetyltransferase criteria provided, single submitter clinical testing A Homozygote Missense variant c.578T>G in Exon 6 of the ACAT1 gene that results in the amino acid substitution p.Met193Arg was identified. The observed variant has a minor allele frequency of 0.00001% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score . Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Pathogenic/ LikelyPathogenic(Variant ID 666490). Experimental studies have shown that this missense change affects ACAT1 function (Abdelkreen et al., 2017).This missense change has been observed in individual(s) with beta-ketothiolase deficiency (Abdelkeem et al., 2019). Based on the above evidence this variant has been classified as Pathogenic according to the ACMG guidelines.
Natera, Inc. RCV000844795 SCV002085829 pathogenic Deficiency of acetyl-CoA acetyltransferase 2020-09-28 no assertion criteria provided clinical testing

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