Combined homozygous HACE1 and TBCD variants in two siblings with severe early-onset neurodevelopmental disorder: Two case reports

Table 2 Computational pathogenicity scores and calibrated thresholds for the tubulin-specific chaperone D c.2139T>A (p.His713Gln) variant

Tool	Score	Prediction	Threshold
AlphaMissense	0.1353	Benign	0-0.33[9]
REVEL	0.162	Benign moderate	0.016-0.183[10]
CADD (v1.7)	0.395 (PHRED)	Benign moderate	0.15-17.3[10]
PolyPhen	0.007	Benign moderate	≤ 0.009[10]
SIFT1	0.01	Indeterminate	0.080-0.327 (benign supporting); 0-0.001 (pathogenic supporting)[10]
PANTHER	30 my (0.13 Pdel)	Probably benign	Time < 200 my[11]

¹SIFT result was flagged as “low confidence” due to limited sequence alignment depth.

PHRED: PHRED-scaled score; Pdel: Probability of deleterious effect; my: Million years.