X-57592419-G-T

Variant names:

• chrX-57592419-G-T
• NM_007157.4:c.371G>T

Variant summary

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

The NM_007157.4(ZXDB):​c.371G>T​(p.Gly124Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000114 in 1,051,309 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 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: 0.000011 (0 hom. 2 hem.)
• Consequence: ZXDB NM_007157.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0860

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=0.073378235).
• BS2: High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZXDB	NM_007157.4	c.371G>T	p.Gly124Val	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.371G>T	p.Gly124Val	missense_variant	Exon 1 of 1	6	NM_007157.4	ENSP00000364023.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.0000114 AC: 12 AN: 1051309 Hom.: 0 Cov.: 34 AF XY: 0.00000594 AC XY: 2 AN XY: 336527

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: 0.0000146

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 27

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 27, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.371G>T (p.G124V) alteration is located in exon 1 (coding exon 1) of the ZXDB gene. This alteration results from a G to T substitution at nucleotide position 371, causing the glycine (G) at amino acid position 124 to be replaced by a valine (V). 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	0.081
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
CADD	Benign	14
DANN	Benign	0.86
DEOGEN2	Benign	0.0086	T
FATHMM_MKL	Benign	0.083	N
LIST_S2	Benign	0.53	T
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-0.61	N
REVEL	Benign	0.020
Sift	Benign	0.12	T
Sift4G	Benign	0.31	T
Polyphen		0.0020	B
Vest4		0.055
MutPred		0.18		Gain of helix (P = 0.0325);
MVP		0.082
MPC		1.3
ClinPred		0.032	T
GERP RS		2.0
Varity_R		0.061
gMVP		0.10

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-57618852;