ClinVar Miner

Submissions for variant NM_000019.4(ACAT1):c.968T>C (p.Ile323Thr)

gnomAD frequency: 0.00002  dbSNP: rs755806238
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Pediatrics, Gifu University RCV000844825 SCV000966102 likely pathogenic Deficiency of acetyl-CoA acetyltransferase 2019-05-05 criteria provided, single submitter research
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002307633 SCV002600347 uncertain significance not specified 2022-10-08 criteria provided, single submitter clinical testing Variant summary: ACAT1 c.968T>C (p.Ile323Thr) results in a non-conservative amino acid change located in the Thiolase, C-terminal domain (IPR020617) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251372 control chromosomes. c.968T>C has been reported in the literature as a presumed compound heterozygous genotype in at-least one individual affected with beta-ketothiolase deficiency (Alpha-Methylacetoacetic Aciduria) (example, Abdelkreem_2017). These data do not allow any conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in 20-25% of normal activity in a tempreature sensitive manner when analyzed in a transient expression system in-vitro (Abdelkreem_2017). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics RCV000844825 SCV004212816 likely pathogenic Deficiency of acetyl-CoA acetyltransferase 2023-08-25 criteria provided, single submitter clinical testing

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