Clinical spectrum and genotype-phenotype correlation of ABCB4 mutations in children: Insights from a North Indian cohort

Table 3 ABCB4 variants in biallelic mutation and their pathogenicity (n = 16)

Patient	Zygosity	Exon number	Mutation	Predicted effect	Domain	Type of mutation	Polyphen	SIFT	Mutation taster	GnomAD1	Updated ACMG class	ACMG criteria
P1	Ho	23	c.2908T>C	p.Phe970Leu	NBD2	MISSENSE	B	D	DC	0	LP	PM1, PM2, PP2
P2 (sibling of P1)	Ho	23	c.2908T>C	p.Phe970Leu	NBD2	MISSENSE	B	D	DC	0	LP	PM1, PM2, PP2
P3	Ho	23	c.2908T>C	p.Phe970Leu	NBD2	MISSENSE	B	D	DC	0	LP	PM1, PM2, PP2
P4	Ho	23	c.2908T>C	p.Phe970Leu	NBD2	MISSENSE	B	D	DC	0	LP	PM1, PM2, PP2
P5	Ho	23	c.2860G>A	p.Gly954Ser	Linker (NBD2 adjacent)	MISSENSE	PossD	D	DC	0	LP	PM1, PM2, PM5, PP2, PP3, PP5
P6 (sibling of P5)	Ho	23	c.2860G>A	p.Gly954Ser	Linker (NBD2 adjacent)	MISSENSE	PossD	D	DC	0	LP	PM1, PM2, PM5, PP2, PP3, PP5
P7	Ho	23	c.2860G>A	p.Gly954Ser	Linker (NBD2 adjacent)	MISSENSE	PossD	D	DC	0	LP	PM1, PM2, PM5, PP2, PP3, PP5
P8	Ho	23	c.2860G>A	p.Gly954Ser	Linker (NBD2 adjacent)	MISSENSE	PossD	D	DC	0	LP	PM1, PM2, PM5, PP2, PP3, PP5
P9	Ho	4	c.139C>T	p.Arg47Ter	TMD1	NONSENSE	-	-	DC	0	P	PVS1, PS4, PM2
P10 (sibling of P9)	Ho	4	c.139C>T	p.Arg47Ter	TMD1	NONSENSE	-	-	DC	0	P	PVS1, PS4, PM2
P11	Ho	25	c.3230C>T	p.Thr1077Met	NBD2	MISSENSE	ProbD	D	DC	0.005	LP	PP2, PP3, PM3
P12	Ho	28	c.3760G>A	p.Gly1254Ser	NBD2	MISSENSE	ProbD	D	DC	0	LP	PP2, PP3, PM3
P13	Ho	15	c.1783C>T	p.Arg595Ter	NBD2 start	NONSENSE	D	D	DC	0.001	P	PVS1, PM2, PP5
P14	Ho	6	c.431G>A	p.Arg144Gln	-	MISSENSE	ProbD	D	DC	0.0007	LP	PM1, PM2, PP2, PP3
P15	Co HET	10	c.1031C>G	p.Ala344Gly	NBD1	MISSENSE	PossD	D	DC	0	LP	PM2, PP2
		19	c.2362C>T	p.Arg788Trp	NBD2	MISSENSE	PossD	D	DC	0.016	LP	PM2, PP2
P16	Co HET	15	c.1783C>T	p.Arg595Ter	NBD2 start	NONSENSE	D	D	DC	0.001	P	PVS1, PM2, PP5
		23	c.2906G>A	p.Arg969His	NBD2	MISSENSE	B	-	Polymorphism	0.0001	LP	PM2, PP2

¹Allele frequency: (1) 0: Strengthens pathogenicity; (2) 0.0001: May support pathogenicity; (3) 0.001: Considered rare; (4) 1%-5%: Unlikely pathogenic; and (5) > 5%: Too common to cause rare disease.

ACMG: American College of Medical Genetics; B: Benign; Co HET: Compound heterozygous; D: Damaging; DC: Mutation taster 1 disease causing; Ho: Homozygous; LP: Likely pathogenic; NBD: Nucleotide binding domain 1; P: Pathogenic; ProbD: Probably damaging; PossD: Possibly damaging; TMD: Transmembrane domain.