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]
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  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
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Variant: NM_001369369.1(FOXN1):c.205C>T (p.Arg69Cys)

CA8459177

322414 (ClinVar)

Gene: FOXN1
Condition: T-cell immunodeficiency, congenital alopecia, and nail dystrophy
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 1f729f1e-5959-4bc2-a604-5fed2095f0ce
Approved on: 2024-07-29
Published on: 2024-07-29

HGVS expressions

NM_001369369.1:c.205C>T
NM_001369369.1(FOXN1):c.205C>T (p.Arg69Cys)
NC_000017.11:g.28524584C>T
CM000679.2:g.28524584C>T
NC_000017.10:g.26851602C>T
CM000679.1:g.26851602C>T
NC_000017.9:g.23875729C>T
NG_007260.1:g.5644C>T
ENST00000577936.2:c.205C>T
ENST00000579795.6:c.205C>T
ENST00000226247.2:c.205C>T
ENST00000481916.6:c.*1196-68475G>A
ENST00000577936.1:c.205C>T
ENST00000579795.5:c.205C>T
NM_003593.2:c.205C>T
NM_003593.3:c.205C>T

Benign

Met criteria codes 2
BA1 BP4
Not Met criteria codes 1
BS3

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 variant NM_001369369.1(FOXN1):c.205C>T is predicted to cause an arginine to cysteine substitution at amino acid position 69. After a comprehensive literature search, the variant has not been identified in any individuals with T-cell immunodeficiency, congenital alopecia, and nail dystrophy. The variant has a gnomAD popmax filtering allele frequency of 0.2496 based upon the Latino population, which is greater than 0.00447 and thus meets BA1. Additionally, the in-silico meta predictor REVEL suggests the variant has no effect on gene function with a score of 0.277, which is less than 0.290 and thus meets BP4. The variant is associated with the following publication: PMID:18006695. In summary, this variant meets criteria to be classified as 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: BP4 and BA1.
Met criteria codes
BA1
The variant has a gnomADv4.0 Grpmax filtering allele frequency of 0.2301 based upon the Admixed American population, which is greater than >0.00447 and thus meets BA1.
BP4
The variant has a REVEL score of 0.277, which is less than 0.290 and thus meets criteria for BP4, suggesting no effect on gene function. Additionally, SpliceAI predicts no impact on splicing (delta scores <=0.01).
Not Met criteria codes
BS3
Arg69Cys retained 91% luciferase activity relative to WT (unpublished data). This variant is one of the Benign validation controls for the assay, which is approved for use as pathogenic evidence only.
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