Genetic Variant ZXDB:p.Ser82Gly (chrX-57592292-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_007157.4(ZXDB):c.244A>G(p.Ser82Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00114 in 1,183,741 control chromosomes in the GnomAD database, including 7 homozygotes. There are 379 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0065 ( 3 hom., 234 hem., cov: 23)

Exomes 𝑓: 0.00059 ( 4 hom. 145 hem. )

Consequence

ZXDB
NM_007157.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.73

Publications

0 publications found

Variant links:

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]

ZXDB links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0033706129).

BP6

Variant X-57592292-A-G is Benign according to our data. Variant chrX-57592292-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3260199.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00647 (715/110559) while in subpopulation AFR AF = 0.0226 (690/30550). AF 95% confidence interval is 0.0212. There are 3 homozygotes in GnomAd4. There are 234 alleles in the male GnomAd4 subpopulation. Median coverage is 23. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 3 gene

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.244A>G	p.Ser82Gly	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.244A>G	p.Ser82Gly	missense	Exon 1 of 1	ENSP00000364023.1	P98169

Frequencies

GnomAD3 genomes

AF:

0.00646

AC:

714

AN:

110516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0226

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00141

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:

0.0000764

Gnomad OTH

AF:

0.00401

GnomAD2 exomes

AF:

0.00119

AC:

153

AN:

128269

AF XY:

0.000752

show subpopulations

Gnomad AFR exome

AF:

0.0221

Gnomad AMR exome

AF:

0.000426

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000365

Gnomad OTH exome

AF:

0.000630

GnomAD4 exome

AF:

0.000593

AC:

636

AN:

1073182

Hom.:

Cov.:

AF XY:

0.000414

AC XY:

145

AN XY:

350546

show subpopulations

African (AFR)

AF:

0.0222

AC:

535

AN:

24142

American (AMR)

AF:

0.000734

AC:

AN:

34049

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18745

East Asian (EAS)

AF:

0.00

AC:

AN:

28438

South Asian (SAS)

AF:

0.0000959

AC:

AN:

52129

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33714

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2857

European-Non Finnish (NFE)

AF:

0.00000480

AC:

AN:

834064

Other (OTH)

AF:

0.00149

AC:

AN:

45044

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

105

131

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00647

AC:

715

AN:

110559

Hom.:

Cov.:

AF XY:

0.00702

AC XY:

234

AN XY:

33357

show subpopulations

African (AFR)

AF:

0.0226

AC:

690

AN:

30550

American (AMR)

AF:

0.00141

AC:

AN:

10651

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2622

East Asian (EAS)

AF:

0.00

AC:

AN:

3397

South Asian (SAS)

AF:

0.00

AC:

AN:

2671

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5894

Middle Eastern (MID)

AF:

0.00

AC:

AN:

212

European-Non Finnish (NFE)

AF:

0.0000764

AC:

AN:

52381

Other (OTH)

AF:

0.00396

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

104

130

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0470

Hom.:

838

Bravo

AF:

0.00756

ESP6500AA

AF:

0.00590

AC:

ESP6500EA

AF:

0.000209

AC:

ExAC

AF:

0.00161

AC:

176

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.049

BayesDel_addAF

Benign

-0.79

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.081

(source)

DANN

Benign

0.46

DEOGEN2

Benign

0.0055

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.37

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-1.7

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

-0.38

REVEL

Benign

0.035

Sift

Benign

0.51

Sift4G

Benign

0.57

Polyphen

0.0

Vest4

0.081

MVP

0.12

MPC

0.97

ClinPred

0.0012

GERP RS

0.64

PromoterAI

-0.17

Neutral

(source)

Varity_R

0.034

gMVP

0.044

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over