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.699+1G>T

CA398322535

536427 (ClinVar)

Gene: FOXN1
Condition: T-cell immunodeficiency, congenital alopecia, and nail dystrophy
Inheritance Mode: Semidominant inheritance
Link to MONDO
UUID: 91559dbe-fe2d-4fc5-b867-cc45d4a084e2
Approved on: 2024-07-29
Published on: 2024-07-29

HGVS expressions

NM_001369369.1:c.699+1G>T
NM_001369369.1(FOXN1):c.699+1G>T
NC_000017.11:g.28527362G>T
CM000679.2:g.28527362G>T
NC_000017.10:g.26854380G>T
CM000679.1:g.26854380G>T
NC_000017.9:g.23878507G>T
NG_007260.1:g.8422G>T
ENST00000577936.2:c.699+1G>T
ENST00000579795.6:c.699+1G>T
ENST00000226247.2:c.699+1G>T
ENST00000481916.6:c.*1196-71253C>A
ENST00000579795.5:c.699+1G>T
NM_003593.2:c.699+1G>T
NM_003593.3:c.699+1G>T
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Uncertain Significance

Met criteria codes 2
PVS1_Moderate PM2_Supporting

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 NM_001369369.1(FOXN1):c.699+1G>T intron 4 donor splice site variant is predicted to result in skipping of exon 4 causing an in frame deletion of Gly197 to Gln233, accounting for 5.7% of the protein (PVS1_Moderate). This variant is absent from gnomADv2.1.1 (PM2_supporting). There is one entry for this variant in ClinVar (SCV000766592.5) but it has not been reported in the literature in individuals with FOXN1-related disease. In summary this variant meets criteria to be classified as uncertain significance for semidominant T-cell immunodeficiency, congenital alopecia, and nail dystrophy due to FOXN1 deficiency based on the ACMG/AMP criteria applied: PVS1_Moderate and PM2_Supporting as specified by the ClinGen SCID VCEP FOXN1 subgroup.
Met criteria codes
PVS1_Moderate
The NM_001369369.1(FOXN1):c.699+1G>T intron 4 donor splice site variant is predicted to result in skipping of exon 4 causing an in frame deletion of Gly197 to Gln233, accounting for 5.7% of the protein. There are 13 missense variants reported as VUS (12) or likely pathogenic (1) in ClinVar within the deleted region. They have not yet been evaluated by the SCID VCEP so are not considered for upgrading PVS1_Strong at this time.
PM2_Supporting
This variant is absent from gnomADv4.0 (PM2_supporting).
Curation History
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