ClinVar Miner

Submissions for variant NM_005857.5(ZMPSTE24):c.794A>G (p.Asn265Ser)

gnomAD frequency: 0.00003  dbSNP: rs281875371
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000128759 SCV002214247 pathogenic not provided 2021-11-05 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 265 of the ZMPSTE24 protein (p.Asn265Ser). There is a small physicochemical difference between asparagine and serine. For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this missense change affects ZMPSTE24 function (PMID: 17152860, 22718200). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). ClinVar contains an entry for this variant (Variation ID: 140540). This missense change has been observed in individual(s) with mandibuloacral dysplasia with lipodystrophy (PMID: 15937076, 17152860, 25629449, 30919593). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs281875371, gnomAD 0.003%).
ZMPSTE24 homepage - Leiden Muscular Dystrophy pages RCV000128759 SCV000172399 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.