The c.307C>T (p.Arg103Cys) variant in JAK3 gene, that encodes for Janus kinase 3, has been reported in in compound heterozygous status with Cys227Profs*49 which is classified as pathogenic by the VCEP, in 1 patient with T-B+NK- SCID (PMID: 34173127) [1 pt]. This variant has also been reported along with R445* (Phase unknown) which is classified as pathogenic by the VCEP, in 1 patient [P073] with T-B+ SCID [0.5 pt]. NK cell data not available (PMID: 28747913). In addition, this variant is reported in compound heterozygous status with c.421-6C>T which is a VUS, in 1 patient [P55] with SCID (PMID: 30778343) [0.25pt]. Also reported in compound heterozygous status with p.Arg117His which is a VUS, in a Patient with T-B+NkLow SCID [0.25pt]. Total 2pts so PM3 met. This variant was found in a patient with T-B+NK- lymphocyte subset profile (PMID: 34173127) [0.5pt], in a patient whose diagnosis of Leaky/Atypical SCID was established (PMID: 30778343) [0.5pt] and in one patient whose Targeted gene panel testing was conducted using NGS and no alternative genetic explanation was found (PMID: 30778343) [1pt]. Total 1.5pts so PP4 met. The GrpMax filtering allele frequency of the European (Non-Finnish) population is 0.00000124 which is less than the threshold <0.000115 so PM2_supporting is met. Therefore, the c.307C>T (p.Arg103Cys) variant in JAK3 gene is classified as likely pathogenic, as per the ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for JAK3 Version 2.3. Evidence: PM3_Strong, PP4, PM2_Supporting