Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Department of Pediatrics, |
RCV000844820 | SCV000966097 | pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2019-05-05 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV000844820 | SCV004296136 | likely pathogenic | Deficiency of acetyl-CoA acetyltransferase | 2023-01-16 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with mitochondrial acetoacetyl-CoA thiolase deficiency (PMID: 28689740). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the ACAT1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ACAT1 are known to be pathogenic (PMID: 7749408). ClinVar contains an entry for this variant (Variation ID: 666512). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |