X-57592169-A-C

Variant names:

• chrX-57592169-A-C
• rs1427159020
• NM_007157.4:c.121A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_007157.4(ZXDB):​c.121A>C​(p.Thr41Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000043 in 1,046,265 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. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00021 (0 hom., 1 hem., cov: 23)
  • Exomes 𝑓: 0.000023 (0 hom. 1 hem.)
• Consequence: ZXDB NM_007157.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0500
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.039331287).

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.121A>C	p.Thr41Pro	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.121A>C	p.Thr41Pro	missense	Exon 1 of 1	ENSP00000364023.1	P98169

Frequencies

GnomAD3 genomes AF: 0.000218 AC: 24 AN: 109904 Hom.: 0 Cov.: 23

Gnomad AFR AF: 0.000728

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000188

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 9997 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000235 AC: 22 AN: 936316 Hom.: 0 Cov.: 30 AF XY: 0.00000338 AC XY: 1 AN XY: 296240

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

African (AFR) AF: 0.000987 AC: 19 AN: 19242

American (AMR) AF: 0.00 AC: 0 AN: 8091

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 12713

East Asian (EAS) AF: 0.00 AC: 0 AN: 21178

South Asian (SAS) AF: 0.00 AC: 0 AN: 33249

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30831

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2423

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 769584

Other (OTH) AF: 0.0000769 AC: 3 AN: 39005

⚠️ 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 AF: 0.000209 AC: 23 AN: 109949 Hom.: 0 Cov.: 23 AF XY: 0.0000306 AC XY: 1 AN XY: 32651

African (AFR) AF: 0.000693 AC: 21 AN: 30298

American (AMR) AF: 0.000188 AC: 2 AN: 10639

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2617

East Asian (EAS) AF: 0.00 AC: 0 AN: 3417

South Asian (SAS) AF: 0.00 AC: 0 AN: 2555

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5791

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 209

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 52264

Other (OTH) AF: 0.00 AC: 0 AN: 1492

Alfa AF: 0.0000843 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	13
DANN	Benign	0.83
DEOGEN2	Benign	0.011	T
FATHMM_MKL	Benign	0.017	N
LIST_S2	Benign	0.37	T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.039	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.050
PrimateAI	Pathogenic	0.87	D
PROVEAN	Benign	-0.33	N
REVEL	Benign	0.036
Sift	Uncertain	0.028	D
Sift4G	Benign	0.21	T
Polyphen		0.0	B
Vest4		0.063
MutPred		0.16		Gain of catalytic residue at P40 (P = 0.0133)
MVP		0.043
MPC		1.4
ClinPred		0.026	T
GERP RS		0.27
PromoterAI		0.074	Neutral
Varity_R		0.14
gMVP		0.069
Mutation Taster		=99/1	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: rs1427159020; hg19: chrX-57618602;