Variant: NM_001369369.1(FOXN1):c.1021C>T (p.Arg341Cys)

CA8459420

439742 (ClinVar)

Gene: FOXN1

Condition: T-cell immunodeficiency, congenital alopecia, and nail dystrophy

Inheritance Mode: Semidominant inheritance

UUID: 73ca275d-88de-4ec4-9c23-55edca86e290

Approved on: 2024-10-25

Published on: 2024-10-25

HGVS expressions

NM_001369369.1:c.1021C>T
NM_001369369.1(FOXN1):c.1021C>T (p.Arg341Cys)
NC_000017.11:g.28534424C>T
CM000679.2:g.28534424C>T
NC_000017.10:g.26861442C>T
CM000679.1:g.26861442C>T
NC_000017.9:g.23885569C>T
NG_007260.1:g.15484C>T
ENST00000577936.2:c.1021C>T
ENST00000579795.6:c.1021C>T
ENST00000226247.2:c.1021C>T
ENST00000481916.6:c.*1195+69627G>A
ENST00000579795.5:c.1021C>T
NM_003593.2:c.1021C>T
NM_003593.3:c.1021C>T

Uncertain Significance

• Met criteria codes: PP3 PM2

• Not Met criteria codes: PP4

Expert Panel

Severe Combined Immunodeficiency Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for FOXN1 Version 1.0.0

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

The variant NM_001369369.1(FOXN1):c.1021C>T is predicted to cause a arginine to cysteine substitution at amino acid position 341. The variant has a Grpmax allele frequency of 0.00001533 based upon the European (Non-Finnish) population, which is less than 0.0000447 (PM2_supporting). The meta predictor Revel predicts a potential disrupting effect on protein function with a score of 0.741, which is greater than 0.644 and thus meets PP3 criteria. The variant was found in the heterozygous state in sample 536 from PMID: 31672859 in a 9 year old patient who displayed TREC copies/μL of 46.3 and was reportedly exome sequenced for SCID related genes (0.5, PP4 not met). In summary this variant meets criteria to be classified as Variant of Uncertain significance- insufficient evidence for semidominant cell immunodeficiency, congenital alopecia, and nail dystrophy due to FOXN1 deficiency based on the ACMG/AMP criteria applied: PP3 and PM2_supporting as specified by the ClinGen SCID VCEP FOXN1 subgroup.

Met criteria codes

• PP3: Variant has a REVEL score of 0.741, which is greater than 0.644 and thus meets PP3 criteria.
• PM2: Variant has a Groupmax filtering allele frequency of 0.00001533 based upon the European (Non-Finnish) population, which is less than 0.0000447 and thus meets PM2_supporting.

Not Met criteria codes

• PP4: The variant was found in the heterozygous state in sample 536 from PMID: 31672859 in a 9 year old patient who displayed TREC copies/μL of 46.3 and was reportedly exome sequenced for SCID related genes (0.5, PP4 not met).