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

Table 5 ABCB4 variants in monoallelic mutations and their pathogenicity (n = 10)

Patient	Zygosity	Exon Number	Mutation	Predicted effect	Domain	Type of mutation	Polyphen	SIFT	Mutation taster	GnomAD1	Updated ACMG class	ACMG criteria
P17 (sibling of P3)	HET	23	c.2908T>C	p.Phe970Leu	NBD2	MISSENSE	B	D	DC	0	VUS	PM1, PM2, PP2
P18 (sibling of P15)	HET	19	c.2362C>T	p.Arg788Trp	NBD2	MISSENSE	ProbD	D	DC	0.016	VUS	PM2, PP2
P19	HET	8	c.808G>C	p.Gly270Arg	TMD1/NBD1 boundary	MISSENSE	ProbD	D	DC	0.189 (THRESHOLD:0.1)	VUS	PS1, PP2, PP3, BS1
P20	HET	8	c.808G>C	p.Gly270Arg	TMD1/NBD1 boundary	MISSENSE	ProbD	D	DC	0.189 (THRESHOLD:0.1)	VUS	PS1, PP2, PP3, BS1
P21	HET	16	c.1963C>G	p.Pro655Ala	NBD2	MISSENSE	B	-	Polymorphism	0	VUS	PP2
P22	HET	14	c.1571C>A	p.Thr524Asn	TMD2	MISSENSE	ProbD	D	DC	0	LP	PS4, PM2, PP3, PP2
P23	HET	9	c.928G>A	p.Ala310Thr	NBD1	MISSENSE	PossD	-	-	-	VUS	-
P24	HET	13	c.1558C>T	p.Gln520Ter	Linker before TMD2	NONSENSE	-	-	-	0.0001	LP	PVS1, PM2
P25	HET	15	c.1650C>A	p.Asn550Lys	TMD2	MISSENSE	PossD	D	-	0.0004	VUS	PM1, PM2, PP2
P26	HET	15	c.1783C>T	p.Arg595Ter	NBD2 start	NONSENSE	-	-	DC	0.001	Pathogenic	PVS1, PM2, PP5

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; D: Damaging; DC: Mutation taster 1 disease causing; HET: Heterozygous; LP: Likely pathogenic; NBD: Nucleotide binding domain 1; ProbD: Probably damaging; PossD: Possibly damaging; TMD: Transmembrane domain 1; VUS: Variant of unknown significance.