ClinVar Miner

Submissions for variant NM_000016.6(ACADM):c.599+1G>A

gnomAD frequency: 0.00001  dbSNP: rs866388216
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000211443 SCV000268443 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
Counsyl RCV000211443 SCV000485329 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-11-18 criteria provided, single submitter clinical testing
Invitae RCV000211443 SCV002230736 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2023-09-27 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 7 of the ACADM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ACADM are known to be pathogenic (PMID: 16121256, 20434380). This variant is present in population databases (no rsID available, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with medium chain acyl-CoA dehydrogenase (MCAD) deficiency (PMID: 20434380). ClinVar contains an entry for this variant (Variation ID: 226060). 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.
Fulgent Genetics, Fulgent Genetics RCV000211443 SCV002808629 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2022-02-23 criteria provided, single submitter clinical testing
Baylor Genetics RCV000211443 SCV004216252 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2023-10-12 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003917863 SCV004731922 likely pathogenic ACADM-related disorder 2024-02-02 criteria provided, single submitter clinical testing The ACADM c.599+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant was not reported in patients with MCAD deficiency. However, a different variant affecting this donor site has been reported, along with the recurrent c.985A>G pathogenic variant, in a patient with biochemical markers consistent with MCAD deficiency (c.599+3A>G; Navarrete et al. 2019. PubMed ID: 30626930). The c.599+1G>A variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-76205796-G-A). Variants that disrupt the consensus splice donor site in ACADM are expected to be pathogenic. This variant is interpreted as likely pathogenic.
Natera, Inc. RCV000211443 SCV001461465 likely pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2020-09-16 no assertion criteria provided clinical testing

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