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Table 3 Variants identified

From: Biallelic variants in COPB1 cause a novel, severe intellectual disability syndrome with cataracts and variable microcephaly

Variant/family no. Variant Predictive tools Conservation gnomAD AF
1 c957+1G>T homozygous
GRCh37:g.14504577C>A
Human Splicing Finder
Donor site loss (− 26.84)
Splice Site Prediction by Neural Network Donor site loss (Mutant score = 0)
MaxEntScan
Donor site loss (− 78.36)
SpliceAI
Donor site loss
New donor site created causing a 1 nucleotide frameshift
  Absent
2 c.1651T>G (p.Phe551Val) homozygous
GRCh37:g.14496127A>C
Polyphen-2 Probably damaging Nucleotide conservation PhyloP 5.21 (strongly conserved) Absent
SIFT Deleterious Amino acid conservation High, to Baker’s Yeast
ConSurf 8/9
CADD (Phred) 32
  1. The variant identified in Family 1 affects the +1 donor position of exon 8. Note the results from SpliceAI which predicts both donor site loss and creation of a new donor site (verified by experimental data in Fig. 2). The missense variant in Family 2 is predicted to be deleterious by a number of tools