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

gnomAD frequency: 0.00089  dbSNP: rs143844274

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen	RCV000547211	SCV005382669	likely benign	T-cell immunodeficiency, congenital alopecia, and nail dystrophy	2024-07-29	reviewed by expert panel	curation	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000547211	SCV000645333	likely benign	T-cell immunodeficiency, congenital alopecia, and nail dystrophy	2024-01-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003905410	SCV004719794	likely benign	FOXN1-related disorder	2019-06-06	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).