chrX-57592432-G-C

Variant names:

• chrX-57592432-G-C
• rs751009121
• NM_007157.4:c.384G>C

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_007157.4(ZXDB):​c.384G>C​(p.Gln128His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000478 in 1,047,061 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000048 (0 hom. 5 hem.)
• Consequence: ZXDB NM_007157.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.37

Genes affected

ZXDB (HGNC:13199): (zinc finger X-linked duplicated B) The ZXDB gene is one of a pair of duplicated zinc finger genes on chromosome Xp11.21 (Greig et al., 1993 [PubMed 8268913]); see also ZXDA (MIM 300235).[supplied by OMIM, Jul 2010]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.07205725).
• BS2: High Hemizygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZXDB	NM_007157.4	c.384G>C	p.Gln128His	missense_variant	Exon 1 of 1	ENST00000374888.3	NP_009088.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZXDB	ENST00000374888.3	c.384G>C	p.Gln128His	missense_variant	Exon 1 of 1	6	NM_007157.4	ENSP00000364023.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000478 AC: 5 AN: 1047061 Hom.: 0 Cov.: 34 AF XY: 0.0000149 AC XY: 5 AN XY: 334701

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000609

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ExAC AF: 0.0000368 AC: 4

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 03, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.384G>C (p.Q128H) alteration is located in exon 1 (coding exon 1) of the ZXDB gene. This alteration results from a G to C substitution at nucleotide position 384, causing the glutamine (Q) at amino acid position 128 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.0098	T
FATHMM_MKL	Benign	0.070	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.072	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.9	L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-0.55	N
REVEL	Benign	0.050
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.088	T
Polyphen		0.0020	B
Vest4		0.075
MutPred		0.087		Loss of phosphorylation at S132 (P = 0.2432);
MVP		0.17
MPC		1.0
ClinPred		0.068	T
GERP RS		2.0
Varity_R		0.10
gMVP		0.16

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs751009121; hg19: chrX-57618865;