. 2024 Feb 6;111(3):487–508. doi: 10.1016/j.ajhg.2024.01.007

Table 2.

Table of ZFX variants

Proband(s)	DNA (GenBank: NC_000023.11)	cDNA (GenBank: NM_003410.4)	Protein (GenBank: NP_003401.2)	CADD score	REVEL score	NMD predicted?	Putative applicable ACMG criteria^a	Consequence	Domain
1, 2	g.24211248C>T	c.(2290C>T)	p.Arg764Trp	25	0.3	–	PM2, PS2⁽²⁾, PP3	missense	ZF12
3, 4, 5	g.24211270C>T	c.(2312C>T)	p.Thr771Met	24.6	0.46	–	PM2, PS2, PP3	missense	ZF12-ZF13 linker
6A–6C, 7	g.24211279A>G	c.(2321A>G)	p.Tyr774Cys	27.3	0.57	–	PM2, PS2⁽⁷⁾, PP3	missense	ZF12-ZF13 linker
8, 9	g.24211315G>A	c.(2357G>A)	p.Arg786Gln	24.6	0.34	–	PM2, PS2⁽⁹⁾, PP3	missense	ZF13
10	g.24207442A>AT	c.(768dup)	p.Lys257^∗	29.3	–	yes	PVS1, PM2	truncation	acidic domain
11	g.24210271G>GT	c.(1319dup)	p.Leu440Phefs^∗21	32	–	no	PVS1_Strong, PS2, PM2	truncation	ZF1
12	g.24209008G>GGA	c.(1205_1206dup)	p.Arg403Glufs^∗12	28.2	–	no	PVS1_Strong, PS2, PM2	truncation	acidic domain
13	g.24210953CAT>C	c.(1996_1997del)	p.Met666Valfs^∗2	32	–	no	PVS1_Strong, PS2, PM2	truncation	ZF9
14	g.24179650G>GT	c.(529dup)	p.Ser177Phefs^∗12	27	–	yes	PVS1, PS2, PM2	truncation	acidic domain
15	g.24179543ATG>A	c.(423_424del)	p.Ser142^∗	25	–	yes	PVS1, PM2	truncation	acidic domain
16	g.24179237CTG>C	c.(115_116del)	p.Val39Phefs^∗14	26.2	–	yes	PVS1, PM2	truncation	N-terminal region

CADD⁵¹ and REVEL⁵² scores were calculated for the missense variants, and putative applicable American College of Medical Genetics (ACMG) criteria are listed.²⁹^,³⁰^,³¹

For criteria that only apply to a subset of probands in each row, the applicable individuals(s) are indicated by superscript. PP3 was applied on the basis of CADD score. According to current ACMG criteria, PVS1 is applied for a gene where loss-of-function is a known mechanism of disease. However, PVS1 was used to upgrade the classification of the truncating variants based on evidence provided in this study.