ClinVar Miner

Submissions for variant NM_000019.4(ACAT1):c.1033_1034del (p.Glu345fs)

dbSNP: rs781496140
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000627576 SCV000748576 pathogenic not provided 2018-04-18 criteria provided, single submitter clinical testing The c.1033_1034delGA variant in the ACAT1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1033_1034delGA variant causes a frameshift starting with codon Glutamic acid 345, changes this amino acid to an Arginine residue, and creates a premature Stop codon at position 9 of the new reading frame, denoted p.Glu345ArgfsX9. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1033_1034delGA variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret c.1033_1034delGA as a pathogenic variant.
Department of Pediatrics, Gifu University RCV000844832 SCV000966110 pathogenic Deficiency of acetyl-CoA acetyltransferase 2019-05-05 criteria provided, single submitter research
Invitae RCV000844832 SCV002130322 pathogenic Deficiency of acetyl-CoA acetyltransferase 2023-07-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Glu345Argfs*9) in the ACAT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACAT1 are known to be pathogenic (PMID: 7749408). This variant is present in population databases (rs781496140, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with beta-ketothiolase deficiency (aka mitochondrial acetoacetyl-CoA thiolase deficiency) (PMID: 28255778). ClinVar contains an entry for this variant (Variation ID: 524080).
Baylor Genetics RCV000844832 SCV004210542 pathogenic Deficiency of acetyl-CoA acetyltransferase 2023-09-09 criteria provided, single submitter clinical testing

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