X-57592446-G-T

Variant names:

• chrX-57592446-G-T
• rs764891813
• NM_007157.4:c.398G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_007157.4(ZXDB):​c.398G>T​(p.Gly133Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 26)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ZXDB NM_007157.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.230

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.061906368).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZXDB	NM_007157.4	c.398G>T	p.Gly133Val	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.398G>T	p.Gly133Val	missense_variant	Exon 1 of 1	6	NM_007157.4	ENSP00000364023.1

Frequencies

GnomAD3 genomes Cov.: 26

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.55e-7 AC: 1 AN: 1047260 Hom.: 0 Cov.: 34 AF XY: 0.00 AC XY: 0 AN XY: 335682

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: 0.0000204

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 26

ExAC AF: 0.00000924 AC: 1

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Sep 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.398G>T (p.G133V) 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 398, causing the glycine (G) at amino acid position 133 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	0.082
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0086	T
FATHMM_MKL	Benign	0.15	N
LIST_S2	Benign	0.61	T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.8	L
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.29	N
REVEL	Benign	0.039
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.014	D
Polyphen		0.029	B
Vest4		0.021
MutPred		0.32		Loss of glycosylation at S132 (P = 0.0493);
MVP		0.082
MPC		1.7
ClinPred		0.098	T
GERP RS		1.3
Varity_R		0.074
gMVP		0.093

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: rs764891813; hg19: chrX-57618879;