Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001369369.1(FOXN1):c.930A>G (p.Thr310=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA8459411

468554 (ClinVar)

Gene: FOXN1

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

Inheritance Mode: Semidominant inheritance

Link to MONDO

UUID: 96ea3c4d-5138-43d8-a589-85e254edf461

Approved on: 2024-07-29

Published on: 2024-07-29

HGVS expressions

NM_001369369.1:c.930A>G

NM_001369369.1(FOXN1):c.930A>G (p.Thr310=)

NC_000017.11:g.28534333A>G

CM000679.2:g.28534333A>G

NC_000017.10:g.26861351A>G

CM000679.1:g.26861351A>G

NC_000017.9:g.23885478A>G

NG_007260.1:g.15393A>G

ENST00000577936.2:c.930A>G

ENST00000579795.6:c.930A>G

ENST00000226247.2:c.930A>G

ENST00000481916.6:c.*1195+69718T>C

ENST00000579795.5:c.930A>G

NM_003593.2:c.930A>G

NM_003593.3:c.930A>G

Likely Benign

BS1 BP7 BP4

Evidence Links 0

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

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_001369369.1(FOXN1):c.930A>G (p.Thr310=) is a synonymous variant. SpliceAI predicts no impact to the splice consensus sequence (delta score 0.00) nor the creation of a new splice site (delta score<=0.01) and the nucleotide is not highly conserved (phyloP score -1.54) (BP4, BP7). The gnomADv2.1.1 PopMax filtering AF is 0.002017 based on 66/24964 alleles in the African/African American population, which is above the >0.00141 threshold for BS1. In summary this variant meets criteria to be classified as likely benign for semidominant T-cell immunodeficiency, congenital alopecia, and nail dystrophy due to FOXN1 deficiency based on the ACMG/AMP criteria applied: BS1, BP4, and BP7 as specified by the ClinGen SCID VCEP FOXN1 subgroup.

BS1

The gnomADv4.0 GrpMax filtering AF is 0.002200 based on 187/75046 alleles in the gnomADv4.0 African/African American population, which is above the >0.00141 threshold for BS1.

BP7

SpliceAI predicts no impact to the splice consensus sequence (delta score 0.00) nor the creation of a new splice site (delta score<=0.01) and the nucleotide is not highly conserved (phyloP score -1.54).

BP4

SpliceAI predicts no impact to the splice consensus sequence (delta score 0.00) nor the creation of a new splice site (delta score<=0.01).

Curation History

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