X-57592251-G-T

Variant names:

• chrX-57592251-G-T
• rs2057894739
• NM_007157.4:c.203G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_007157.4(ZXDB):​c.203G>T​(p.Gly68Val) 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. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G68D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.5e-7 (0 hom. 0 hem.)
  • Failed GnomAD Quality Control
• Consequence: ZXDB NM_007157.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19816226).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007157.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZXDB	NM_007157.4	MANE Select	c.203G>T	p.Gly68Val	missense	Exon 1 of 1	NP_009088.1	P98169

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZXDB	ENST00000374888.3	TSL:6 MANE Select	c.203G>T	p.Gly68Val	missense	Exon 1 of 1	ENSP00000364023.1	P98169

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 9.51e-7 AC: 1 AN: 1051749 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 340941

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 22853

American (AMR) AF: 0.00 AC: 0 AN: 30755

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18072

East Asian (EAS) AF: 0.00 AC: 0 AN: 25881

South Asian (SAS) AF: 0.00 AC: 0 AN: 49931

European-Finnish (FIN) AF: 0.0000306 AC: 1 AN: 32647

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2793

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 824655

Other (OTH) AF: 0.00 AC: 0 AN: 44162

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 23

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.088
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	18
DANN	Benign	0.96
DEOGEN2	Benign	0.0087	T
FATHMM_MKL	Benign	0.30	N
LIST_S2	Benign	0.46	T
M_CAP	Pathogenic	0.57	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.2
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.12	N
REVEL	Benign	0.012
Sift	Uncertain	0.0060	D
Sift4G	Uncertain	0.014	D
Polyphen		0.32	B
Vest4		0.10
MutPred		0.18		Loss of methylation at R67 (P = 0.0455)
MVP		0.15
MPC		1.8
ClinPred		0.15	T
GERP RS		1.4
PromoterAI		-0.084	Neutral
Varity_R		0.11
gMVP		0.072
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs2057894739; hg19: chrX-57618684;