ClinVar Miner

Submissions for variant NM_000016.5(ACADM):c.469-9A>G (rs181322317)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000211511 SCV000268505 benign Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
GeneDx RCV000251406 SCV000526101 likely benign not specified 2017-02-21 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Integrated Genetics/Laboratory Corporation of America RCV000251406 SCV000918380 likely benign not specified 2018-09-10 criteria provided, single submitter clinical testing Variant summary: ACADM c.469-9A>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00074 in 262480 control chromosomes, predominantly within the African subpopulation at a frequency of 0.0074 in the gnomAD database. The observed variant frequency within African control individuals is slightly higher than the estimated maximal expected allele frequency for a pathogenic variant in ACADM causing Medium Chain Acyl-CoA Dehydrogenase Deficiency phenotype (0.0054), suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.469-9A>G in individuals affected with Medium Chain Acyl-CoA Dehydrogenase Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000211511 SCV000630288 benign Medium-chain acyl-coenzyme A dehydrogenase deficiency 2017-04-28 criteria provided, single submitter clinical testing
PreventionGenetics RCV000251406 SCV000301505 likely benign not specified criteria provided, single submitter clinical testing

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