ClinVar Miner

Submissions for variant NM_000019.4(ACAT1):c.826+3_826+6del

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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 RCV002726398 SCV003004892 uncertain significance Deficiency of acetyl-CoA acetyltransferase 2022-04-28 criteria provided, single submitter clinical testing This sequence change falls in intron 8 of the ACAT1 gene. It does not directly change the encoded amino acid sequence of the ACAT1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs754619277, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ACAT1-related conditions. 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Unidad De Genómica, Hospital Infantil Universitario Niño Jesús RCV002726398 SCV005402680 likely pathogenic Deficiency of acetyl-CoA acetyltransferase 2024-11-21 criteria provided, single submitter clinical testing This variant is located at the initial part of intron 8 changing the third to sixth nucleotide, it has a very low frequency (<0.002%) in gnomAD, with no homozygous in general population (PM2). The position is conserved: phyloP = 9.7 is between 7.52 and 9.88 (PP3). Is in trans with a known pathogenic variant (PM3). This variant is present in a year old female, altered newborn screening (C5:1 = 0.1 µmol/L y C3DCC4OH=1.59 µmol/L.), increased urinary excretion of 2-methyl-3-hydroxybutyrate (741 mmol/creat mol NV: 0-18 mmol/creat mol), 2- methylacetoacetate (10 mmol/creat mol NV: undetectable) and tiglylglycine (83 mmol/creat mol NV: 0-3 mmol/creat mol) (PP4). Sequencing cDNA demonstrated exon skipping (not published) (PS3)

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