Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003523638 | SCV004304798 | pathogenic | Polyglandular autoimmune syndrome, type 1 | 2023-07-13 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individuals with autosomal recessive autoimmune polyendocrinopathy syndrome (PMID: 27105486, 31420020). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 9 of the AIRE 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 AIRE are known to be pathogenic (PMID: 11524731, 26141571). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |