ClinVar Miner

Submissions for variant NM_000444.6(PHEX):c.349+1G>C

dbSNP: rs193922459
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
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000030357 SCV000053024 likely pathogenic Familial X-linked hypophosphatemic vitamin D refractory rickets 2011-08-18 criteria provided, single submitter curation Converted during submission to Likely pathogenic.
GeneDx RCV000486450 SCV000570862 likely pathogenic not provided 2016-07-26 criteria provided, single submitter clinical testing The c.349+1 G>C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. While this variant destroys the canonical splice donor site in intron 3, the adjacent exon 3 remains in-frame. In the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Labcorp Genetics (formerly Invitae), Labcorp RCV000486450 SCV004509443 pathogenic not provided 2023-01-05 criteria provided, single submitter clinical testing 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 disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 36678). Disruption of this splice site has been observed in individuals with hypophosphatemia (PMID: 10737991, 30682568). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the PHEX gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PHEX are known to be pathogenic (PMID: 9097956, 9106524, 19219621).

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.