Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genomic Research Center, |
RCV000002979 | SCV000746954 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2017-12-18 | criteria provided, single submitter | clinical testing | |
| Department of Pediatrics, |
RCV000002979 | SCV000966103 | likely pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2019-05-05 | criteria provided, single submitter | research | |
| Invitae | RCV000002979 | SCV001236935 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2021-12-09 | criteria provided, single submitter | clinical testing | 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: "Benign"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ACAT1 function (PMID: 7749408). ClinVar contains an entry for this variant (Variation ID: 2845). This missense change has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 9744475, 28875337; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs120074147, gnomAD 0.06%). This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 333 of the ACAT1 protein (p.Ala333Pro). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000002979 | SCV004021122 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2023-06-09 | criteria provided, single submitter | clinical testing | Variant summary: ACAT1 c.997G>C (p.Ala333Pro) results in a non-conservative amino acid change located in the C-terminal domain (IPR020617) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251382 control chromosomes (gnomAD, v2.1 Exomes dataset). c.997G>C has been reported in the literature in many compound heterozygous individuals, primarily of East Asian ancestry, affected with Alpha-Methylacetoacetic Aciduria (e.g., Fukao_1995, Fukao_1998, Su_2017, Lin_2021). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant displayed no residual enzymatic activity (e.g., Fukao_1995, Fukao_1998). The following publications have been ascertained in the context of this evaluation (PMID: 9744475, 7749408, 34001203, 28875337). Three ClinVar submitters (evaluation after 2014) have cited the variant, and all submitters classified the variant as pathogenic (n = 2) or likely pathogenic (n = 1). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Baylor Genetics | RCV000002979 | SCV004212805 | likely pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2023-09-05 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000002979 | SCV000023137 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 1998-01-01 | no assertion criteria provided | literature only |