Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_001369369.1(FOXN1):c.1757G>A (p.Cys586Tyr)

CA8459619

468551 (ClinVar)

Gene: FOXN1
Condition: T-cell immunodeficiency, congenital alopecia, and nail dystrophy
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 7905efb1-d2a5-4cc8-a3d1-e15c6403b221
Approved on: 2024-07-29
Published on: 2024-07-29

HGVS expressions

NM_001369369.1:c.1757G>A
NM_001369369.1(FOXN1):c.1757G>A (p.Cys586Tyr)
NC_000017.11:g.28537246G>A
CM000679.2:g.28537246G>A
NC_000017.10:g.26864264G>A
CM000679.1:g.26864264G>A
NC_000017.9:g.23888391G>A
NG_007260.1:g.18306G>A
ENST00000577936.2:c.1757G>A
ENST00000579795.6:c.1757G>A
ENST00000226247.2:c.1757G>A
ENST00000481916.6:c.*1195+66805C>T
ENST00000579795.5:c.1757G>A
NM_003593.2:c.1757G>A
NM_003593.3:c.1757G>A
More

Likely Benign

Met criteria codes 1
BS1
Not Met criteria codes 2
PP3 BP4

Evidence Links 0

Expert Panel

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

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Severe Combined Immunodeficiency Disease VCEP
The missense variant NM_001369369.1(FOXN1):c.1757G>A (p.Cys586Tyr) has a gnomADv3.1.2 popmax filtering allele frequency of 0.003485 based upon the African/African American population (165/41444 alleles), which is above the BS1 threshold of >0.00141 but below the BA1 threshold of >0.00447 and thus meets BS1. After a comprehensive literature search, the variant has not been identified in any individuals with T-cell immunodeficiency, congenital alopecia, and nail dystrophy. In summary, this variant meets criteria to be classified as likely benign for semidominant T-cell immunodeficiency, congenital alopecia, and nail dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BS1.
Met criteria codes
BS1
The variant has a gnomADv4.0 Grpmax filtering allele frequency of 0.003841 based upon the African/African American population (317/75040 alleles), which is above the BS1 threshold of >0.00141 but below the BA1 threshold of >0.00447 and thus meets BS1.
Not Met criteria codes
PP3
This variant has a REVEL score of 0.607, below the PP3 threshold of ≥0.644 but above the the BP4 threshold of <0.290. Additionally, SpliceAI predicts no impact on splicing (delta scores 0.00).
BP4
This variant has a REVEL score of 0.607, below the PP3 threshold of ≥0.644 but above the the BP4 threshold of <0.290.
Curation History
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