ClinVar Miner

Submissions for variant NM_018668.4(VPS33B):c.1225+5G>C (rs398122407)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000599157 SCV000706926 pathogenic not provided 2017-09-22 criteria provided, single submitter clinical testing
GeneDx RCV000599157 SCV000709994 likely pathogenic not provided 2018-01-30 criteria provided, single submitter clinical testing The c.1225+5G>C variant in the VPS33B gene has been reported previously in multiple unrelated individuals with an attenuated arthrogryposis, renal dysfunction, and cholestasis (ARC) syndrome (Smith et al., 2012; Weyand et al., 2016). This variant reduces the quality of the splice donor site in intron 16, and is expected to cause abnormal gene splicing. Functional studies demonstrated that the shorter protein product of the c.1225+5G>C variant retained some ability to interact with VIPAR, and thus it retained partial wild-type function (Smith et al., 2012). The c.1225+5G>C variant is observed in 4/33582 (0.012%) alleles from individuals of Latino background, 5/246220 (0.002%) alleles in large population cohorts, and no individuals were reported to be homozygous (Lek et al., 2016). We interpret c.1225+5G>C as a likely pathogenic variant.
Ambry Genetics RCV000624476 SCV000742493 likely pathogenic Inborn genetic diseases 2017-05-25 criteria provided, single submitter clinical testing
OMIM RCV000074446 SCV000108462 pathogenic Arthrogryposis, renal dysfunction, and cholestasis 1 2012-12-01 no assertion criteria provided literature only

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.