Table 1

Candidate variants identified in this study

GeneMutation cDNAProteinPatientGnomAD NFE AFCADDGERPReferenceACMG class
SIGMAR1 c.412G>Ap.Glu138LysA: II,1; II,2028.34.74
SIGMAR1 c.352+1G>ASplicing, p.?Pt 1028.25.044
ARHGEF28 c.1424G>Cp.Arg475ThrB: II,1; II,29.72E−0622.76.073
ARHGEF28 c.4374T>Gp.Cys1458TrpB: II,1; II,2013.55−7.953
ARHGEF28 c.4647G>A last nucleotide of exon p.Glu1549GluPt 20.00015994.6914.193
ARHGEF28 c.5122C>Gp.Leu1708ValPt 2017.842.973
VRK1 c.961C>Tp.Arg321CysC: II,1; II,24.49E−0524.65.13 20 3
PNKP c.1295_1298+6delSplicing, p.?D: II,1; II,2; II,35.68E−05333.415
PNKP c.148C>Gp.Gln50GluD: II,1; II,2; II,38.96E−0626.15.434
KBTBD13 c.164C>Gp.Ala55GlyE: II,2; II,3012.964.64
GNE c.2116T>Cp.Tyr706HisF: II,1; II,2; II,32.686E−0527.55.57 28 4
GNE c.98A>Gp.Glu33GlyF: II,1; II,2; II,3023.55.13 29 4
AGRN c.2971C>Tp.Leu991PheG: III,1; III,20.00013739.6441.434
AGRN c.3404A>Gp.Gln1135ArgG: III,1; III,20.00832623.74.164
  • CADD scores: scaled CADD scores (Phred like) for scoring deleteriousness.

  • GERP scores: GERP conservation score of aminoacidic residues across different species. ACMG (American College of Medical Genetics) guidelines.43

  • GnomAD, allele frequency aggregated database; NFE, Non-Finnish European.