Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Natera, |
RCV000844765 | SCV007530747 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2024-09-05 | criteria provided, single submitter | clinical testing | The c.1A>G variant in ACAT1 is predicted to result in start loss due to disruption of the initiator methionine. This variant is expected to result in nonsense mediated decay, truncation, or a dysfunctional protein product. This variant is rare in the general population with a frequency below the threshold expected for the associated phenotype(s). This variant has been observed in one or more individuals affected with the associated recessive disease, as either homozygous or compound heterozygous with a second variant (PMID: 28220263). Given the available evidence, this variant is classified as Pathogenic. |
| Fulgent Genetics, |
RCV000844765 | SCV005680506 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2024-05-11 | criteria provided, single submitter | clinical testing | |
| Neuberg Centre For Genomic Medicine, |
RCV000844765 | SCV004101482 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | criteria provided, single submitter | clinical testing | The initiator codon variant p.M1V in ACAT1 (NM_000019.4) has been previously reported in individuals affected with mitochondrial acetoacetyl-CoA thiolase (T2) deficiency (Abdelkreem et al, 2019; Nguyen et al, 2017). The variant is reported to have reduced translational efficiency (11%) (Fukao, Matsuo, et al, 2003). The p.M1V variant is has a gnomAD frequency of 0.0006620 %. The p.M1V variant is a loss of function variant in the gene ACAT1, which is intolerant of Loss of Function variants. The variant is predicted to be damaging by SIFT and the residue is conserved across species. The nucleotide change in ACAT1 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Pathogenic.The observed variant has also been detected in the spouse in heterozygous state. | |
| Labcorp Genetics |
RCV000844765 | SCV002242456 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2025-11-05 | criteria provided, single submitter | clinical testing | This sequence change affects the initiator codon of the ACAT1 mRNA. This change may impact translation initiation or efficiency. The next in-frame methionine is located at codon 91. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of the initiator codon has been observed in individual(s) with beta-ketothiolase deficiency (PMID: 12754704, 28220263). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 666460). Algorithms developed to predict the effect of variants on gene product structure and function are not available or were not evaluated for this variant. Experimental studies have shown that disruption of the initiator codon affects ACAT1 function (PMID: 12754704). For these reasons, this variant has been classified as Pathogenic. |
| Department of Pediatrics, |
RCV000844765 | SCV000966029 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2019-05-05 | criteria provided, single submitter | research |