ClinVar Miner

Submissions for variant NM_000019.4(ACAT1):c.1163+1G>A

gnomAD frequency: 0.00001  dbSNP: rs1423476705
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001385168 SCV001584931 pathogenic Deficiency of acetyl-CoA acetyltransferase 2024-01-16 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 11 of the ACAT1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (no rsID available, gnomAD 0.002%). Disruption of this splice site has been observed in individual(s) with beta-ketothiolase deficiency (Invitae). 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: 1072442). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the ACAT1 protein in which other variant(s) (p.Gly418Asp) have been observed in individuals with ACAT1-related conditions (PMID: 28689740). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV001385168 SCV005059085 likely pathogenic Deficiency of acetyl-CoA acetyltransferase 2023-12-07 criteria provided, single submitter clinical testing

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