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

Table 3 Variants identified

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	Amino acid conservation	High, to Baker’s Yeast ConSurf 8/9

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

ISSN: 1756-994X