ClinVar Miner

Submissions for variant NM_000016.6(ACADM):c.85C>T (p.Arg29Ter)

gnomAD frequency: 0.00001  dbSNP: rs745793409
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192881 SCV001361311 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2022-05-19 criteria provided, single submitter clinical testing Variant summary: ACADM c.85C>T (p.Arg29X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 251424 control chromosomes. c.85C>T has been reported in the literature in at least one homozygous individual and one compound heterozygyous individual with Medium Chain Acyl-CoA Dehydrogenase Deficiency (Derks_2006, Strum_2012). In comparison to healthy controls, a patient homozygous for the variant had 6% residual protein activity, suggesting the variant impairs protein function (Strum_2012). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae RCV001192881 SCV003523309 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2022-09-03 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 928650). This premature translational stop signal has been observed in individual(s) with MCAD deficiency (PMID: 16737882, 23028790). This variant is present in population databases (rs745793409, gnomAD 0.006%). This sequence change creates a premature translational stop signal (p.Arg29*) in the ACADM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ACADM are known to be pathogenic (PMID: 16121256, 20434380).
Baylor Genetics RCV001192881 SCV004217267 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2023-03-30 criteria provided, single submitter clinical testing
Natera, Inc. RCV001192881 SCV002092795 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-03-17 no assertion criteria provided clinical testing

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