ClinVar Miner

Submissions for variant NM_001253852.3(AP4B1):c.1216C>T (p.Arg406Ter) (rs776976178)

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 RCV000485345 SCV000571543 likely pathogenic not provided 2016-09-12 criteria provided, single submitter clinical testing The R406X variant in the AP4B1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R406X variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R406X variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000505223 SCV001387457 pathogenic Spastic paraplegia 47, autosomal recessive 2019-08-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg406*) in the AP4B1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs776976178, ExAC 0.02%). This variant has been observed in combination with another AP4B1 variant in individuals affected with hereditary spastic paraplegia (PMID: 29193663). ClinVar contains an entry for this variant (Variation ID: 422147). Loss-of-function variants in AP4B1 are known to be pathogenic (PMID: 22290197, 24700674, 24781758). For these reasons, this variant has been classified as Pathogenic.
Molecular Genetics Laboratory,BC Children's and BC Women's Hospitals RCV000505223 SCV000599242 likely pathogenic Spastic paraplegia 47, autosomal recessive 2017-01-04 no assertion criteria provided clinical testing

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.