ClinVar Miner

Submissions for variant NM_005857.5(ZMPSTE24):c.1204-1G>A

gnomAD frequency: 0.00001  dbSNP: rs61751009
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000128725 SCV000517014 pathogenic not provided 2015-05-26 criteria provided, single submitter clinical testing The c.1204-1 G>A variant in the ZMPSTE24 gene has been reported previously in two compoundheterozygous siblings of Turkish ancestry diagnosed with mandibulo-acral dysplasia (Navarro et al., 2014). This splice site variant destroys the canonical splice acceptor site in intron 9. It is predicted to causeabnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1204-1G>A variant was not observed in approximately 6,500 individuals of European and African American ancestryin the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.We interpret c.1204-1 G>A as a pathogenic variant.
Invitae RCV000128725 SCV004291788 likely pathogenic not provided 2023-10-03 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 9 of the ZMPSTE24 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs61751009, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with Mandibulo-acral dysplasia (PMID: 24169522). 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: 140513). 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. 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.
ZMPSTE24 homepage - Leiden Muscular Dystrophy pages RCV000128725 SCV000172365 not provided not provided no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.