ClinVar Miner

Submissions for variant NM_001369369.1(FOXN1):c.1420C>T (p.Gln474Ter)

dbSNP: rs1438890364
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
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV000818184 SCV005382652 pathogenic T-cell immunodeficiency, congenital alopecia, and nail dystrophy 2024-07-29 reviewed by expert panel curation NM_001369369.1(FOXN1):c.1420C>T (p.Gln474Ter) is a nonsense variant in exon 8, of 9, which is predicted to undergo NMD (PVS1). This variant was reported in P20 (PMID: 31447097) with nail dystrophy, low TRECs, and low CD8 cell counts 488 cells/ul [nv:560-1700], which together is highly specific for FOXN1 related disease (PP4). This variant is absent from gnomADv2.1.1 (PM2_supporting). In summary this variant meets criteria to be classified as pathogenic for semidominant T-cell immunodeficiency, congenital alopecia, and nail dystrophy due to FOXN1 deficiency based on the ACMG/AMP criteria applied: PVS1, PM2_supporting, and PP4 as specified by the ClinGen SCID VCEP FOXN1 subgroup.
Labcorp Genetics (formerly Invitae), Labcorp RCV000818184 SCV000958783 pathogenic T-cell immunodeficiency, congenital alopecia, and nail dystrophy 2023-04-30 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: 660886). This premature translational stop signal has been observed in individual(s) with clinical features of FOXN1 haploinsufficiency (PMID: 31447097). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln474*) in the FOXN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FOXN1 are known to be pathogenic (PMID: 10206641, 15180707, 31447097).
Baylor Genetics RCV000818184 SCV001521234 pathogenic T-cell immunodeficiency, congenital alopecia, and nail dystrophy 2019-03-26 criteria provided, single submitter clinical testing This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].

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.