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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