Table 3.

Rare variants identified in EPHA2, FOXI1 and KCNJ10

Case	Class	Gene	Transcript	cDNA	Protein	In-house AF (%)	gnomAD AF (%)	CADD_PHRED	SIFT	PPH2	Mutation Taster	SpliceAI	ACMG
SLC017	M0	EPHA2	NM_004431.4	c.2627G > A	p.(Arg876His)	2.36	1.70	32	0	0.769	NA	0.03	UV2
SLC039	M0/CEVA	FOXI1	NM_012188.4	c.677C > T	p.(Thr226Ile)	0.56	0.37	11	0.14	0.109	P	0.03	UV2
SLC052	M0	EPHA2	NM_004431.4	c.1941G > T	p.(Thr647 =)	1.09	0.55	7.309	NA	NA	NA	0.05	UV2
SLC052	M0	EPHA2	NM_004431.4	c.1896G > A	p.(Leu632 =)	0.76	0.05	3.197	NA	NA	NA	0.05	UV2
SLC052	M0	FOXI1	NM_012188.4	c.677C > T	p.(Thr226Ile)	0.56	0.37	11	0.14	0.109	P	0.03	UV2
SLC069	M0	FOXI1	NM_012188.4	c.677C > T	p.(Thr226Ile)	0.56	0.37	11	0.14	0.109	P	0.03	UV2

Available sequencing datasets of monoallelic (M1, M0/CEVA) and zeroallelic (M0) individuals were screened for variants in EPHA2, FOXI1 and KCNJ10 with an allele frequency of ≤ 5% in gnomAD (V.2.1.1). Scores that meet the thresholds for pathogenicity as described in the methods section are indicated in bold

In-house AF allele frequency (%) in in-house database (~ 7500 exomes), GnomAD AF allele frequency (%) in gnomAD database V.2.1.1, CADD_PHRED Combined Annotation Dependent Depletion PHRED score, SIFT Scale-Invariant Feature Transform, PPH2 PolyPhen-2 score, MutationTaster (prob) MutationTaster score with probability (0–1), spliceAI splicing prediction score, ACMG variant classification according to the American College of Medical Genetics and Genomics (ACMG) classification guidelines (Oza et al. 2018), UV2 likely benign, NA not available, P polymorphism