ClinVar Miner

Submissions for variant NM_001369369.1(FOXN1):c.382C>T (p.Arg128Trp)

gnomAD frequency: 0.00210  dbSNP: rs144301161
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV000767976 SCV005382694 likely benign T-cell immunodeficiency, congenital alopecia, and nail dystrophy 2024-10-25 reviewed by expert panel curation The variant NM_001369369.1(FOXN1):c.382C>T (p.Arg128Trp) is predicted to cause an arginine to tryptophan substitution at amino acid position 128. The variant has a Grpmax allele frequency of 0.005950 based upon the gnomADv4.0 African American subpopulation, which is greater than 0.00447 and thus meets BA1 criteria. The meta predictor Revel predicts a score of 0.616, which is less than 0.644 and greater than 0.290, which does not meet BP4 or PP3 criteria. The variant was found in the heterozygous state in sample 336 from PMID: 31672859 who displayed isolated phenotypes such as low TRECs and low CD4+ count (PP4 not met). In summary this variant meets criteria to be classified as benign for semidominant cell immunodeficiency, congenital alopecia, and nail dystrophy due to FOXN1 deficiency based on the ACMG/AMP criteria applied: BA1 as specified by the ClinGen SCID VCEP FOXN1 subgroup, however the ClinGen SCID VCEP has modified the classification to Likely Benign due to the suspicious patient and the remaining possibility that the variant could be associated with isolated immunologic phenotypes such as low TRECs.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767976 SCV000898718 uncertain significance T-cell immunodeficiency, congenital alopecia, and nail dystrophy 2017-12-20 criteria provided, single submitter clinical testing FOXN1 NM_003593.2 exon 2 p.Arg128Trp (c.382C>T): This variant has not been reported in the literature but is present in 0.6% (152/23736) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs144301161). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp RCV000767976 SCV001729894 benign T-cell immunodeficiency, congenital alopecia, and nail dystrophy 2024-12-16 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV003224404 SCV003919987 uncertain significance T-cell immunodeficiency, congenital alopecia, and nail dystrophy; T-cell lymphopenia, infantile, with or without nail dystrophy, autosomal dominant 2021-03-30 criteria provided, single submitter clinical testing FOXN1 NM_003593 exon 2 p.Arg128Trp (c.382C>T): This variant has not been reported in the literature but is present in 0.6% (152/23736) of African alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs144301161). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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