Total submissions: 2
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 - |
RCV000128759 | SCV000172399 | not provided | not provided | no assertion provided | not provided |