ClinVar Miner

Submissions for variant NM_000016.6(ACADM):c.449_452del (p.Thr150fs)

dbSNP: rs786204642
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000169427 SCV000268448 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
Invitae RCV000169427 SCV000630287 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2024-01-26 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Thr150Argfs*4) 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). This variant is present in population databases (rs757500332, gnomAD 0.03%). This premature translational stop signal has been observed in individuals with MCAD deficiency (PMID: 15915086, 19064330, 22796001, 25503862). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 189036). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Eurofins Ntd Llc (ga) RCV000723370 SCV000700258 pathogenic not provided 2017-03-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000169427 SCV001361312 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2019-09-09 criteria provided, single submitter clinical testing Variant summary: ACADM c.449_452delCTGA (p.Thr150ArgfsX4) 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. The variant allele was found at a frequency of 2e-05 in 251336 control chromosomes (gnomAD). c.449_452delCTGA has been reported in the literature in compound heterozygous and homozygous individuals affected with Medium Chain Acyl-CoA Dehydrogenase Deficiency (Ensenauer_2005, Purevsuren_2009). These data indicate that the variant is very likely to be associated with disease. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Beijing Key Laboratry for Genetics of Birth Defects, Beijing Children's Hospital RCV000169427 SCV001739490 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2020-02-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV000169427 SCV004212147 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2023-10-28 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000723370 SCV004220052 pathogenic not provided 2022-12-22 criteria provided, single submitter clinical testing This frameshift variant alters the translational reading frame of the ACADM mRNA and causes the premature termination of ACADM protein synthesis. The frequency of this variant in the general population, 0.00027 (5/18392 chromosomes, http://gnomad.broadinstitute.org), is consistent with pathogenicity. In the published literature, the variant has been reported in individuals with medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (PMID: 15915086 (2005), 19064330 (2009), 21239873 (2011), 22796001 (2012), 25503862 (2015), 27856190 (2016), and 33841490 (2021)). Based on the available information, this variant is classified as pathogenic.
Counsyl RCV000169427 SCV000220837 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2018-02-22 no assertion criteria provided clinical testing
OMIM RCV000169427 SCV001786673 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2024-04-04 no assertion criteria provided literature only
Natera, Inc. RCV000169427 SCV002092829 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-03-17 no assertion criteria provided clinical testing
Developmental and Behavioral Pediatrics, First Affiliated Hospital of Jilin University RCV000169427 SCV003838957 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency no assertion criteria provided clinical testing
Neonatal Disease Screening Center, Medical Genetics Center, Huaihua City Maternal and Child Health Care Hospital RCV000169427 SCV004800880 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency no assertion criteria provided clinical testing PVS1+PM2_P+PM3+PP4

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