ClinVar Miner

Submissions for variant NM_014049.5(ACAD9):c.151-1_151del

dbSNP: rs766026673
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001052315 SCV001216520 likely pathogenic not provided 2023-11-20 criteria provided, single submitter clinical testing This variant results in the deletion of part of exon 2 (c.151-1_151del) of the ACAD9 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 ACAD9 are known to be pathogenic (PMID: 25721401). This variant is present in population databases (rs766026673, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ACAD9-related conditions. ClinVar contains an entry for this variant (Variation ID: 848539). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002282438 SCV002570854 likely pathogenic Mitochondrial complex I deficiency 2022-07-14 criteria provided, single submitter clinical testing Variant summary: ACAD9 c.151-1_151delGA is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a canonical 3 acceptor site and creates a new cryptic exonic one, resulting in the deletion of part of exon 2. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 249802 control chromosomes (gnomAD). To our knowledge, no occurrence of c.151-1_151delGA in individuals affected with Mitochondrial Complex I Deficiency, Nuclear Type 20 and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV001275863 SCV004207030 likely pathogenic Acyl-CoA dehydrogenase 9 deficiency 2023-10-31 criteria provided, single submitter clinical testing
Natera, Inc. RCV001275863 SCV001461495 likely pathogenic Acyl-CoA dehydrogenase 9 deficiency 2020-09-16 no assertion criteria provided clinical testing

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