Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001733378 | SCV001983543 | likely pathogenic | Severe combined immunodeficiency disease | 2021-09-02 | criteria provided, single submitter | clinical testing | Variant summary: PGM3 c.70C>T (p.Gln24X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 130570 control chromosomes. To our knowledge, no occurrence of c.70C>T in individuals affected with Severe Combined Immunodeficiency Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. However, a different variant upstream of this one, namely c.61C>T, translating to p.Gln21X (p.Gln21*) has been submitted with a clinical-significance assessment as pathogenic by one clinical diagnostic laboratory to ClinVar after2014. Additionally, at-least one truncation downstream of this position (c.394A>T, p.R132*) has been reported in the HGMD database. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Center for Genomic Medicine, |
RCV003493871 | SCV004243270 | likely pathogenic | not provided | 2024-02-06 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003746597 | SCV004475175 | pathogenic | Immunodeficiency 23 | 2023-06-09 | 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: 1301339). This variant has not been reported in the literature in individuals affected with PGM3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln24*) in the PGM3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PGM3 are known to be pathogenic (PMID: 17548465, 24589341, 24931394). |