ClinVar Miner

Submissions for variant NM_000016.6(ACADM):c.388-3T>G

gnomAD frequency: 0.00004  dbSNP: rs764942250
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000211465 SCV000268464 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2015-02-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000211465 SCV000630284 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2024-01-26 criteria provided, single submitter clinical testing This sequence change falls in intron 5 of the ACADM gene. It does not directly change the encoded amino acid sequence of the ACADM protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs764942250, gnomAD 0.02%). This variant has been observed in individual(s) with medium-chain acyl-coenzyme A dehydrogenase deficiency (PMID: 20434380). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 226079). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.
Counsyl RCV000211465 SCV000799576 uncertain significance Medium-chain acyl-coenzyme A dehydrogenase deficiency 2018-04-27 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV001800539 SCV002047267 likely pathogenic not provided 2020-09-17 criteria provided, single submitter clinical testing The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function.
Baylor Genetics RCV000211465 SCV004216230 pathogenic Medium-chain acyl-coenzyme A dehydrogenase deficiency 2023-12-28 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003907787 SCV004736086 uncertain significance ACADM-related disorder 2024-02-13 no assertion criteria provided clinical testing The ACADM c.388-3T>G variant is predicted to interfere with splicing. This variant was reported in the compound heterozygous state in patient with high levels of hexanoylglycine (C6) suggestive of MCAD deficiency. However, clinical information as well as levels for C8 and C10 organic acids were not provided (Smith et al. 2010. PubMed ID: 20434380). This variant is reported in 0.020% of alleles in individuals of Latino descent in gnomAD. This variant is predicted to affect splicing. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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