Genetic Variant ZXDB:p.Thr78Pro (chrX-57592280-A-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007157.4(ZXDB):c.232A>C(p.Thr78Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000526 in 1,179,841 control chromosomes in the GnomAD database, including 2 homozygotes. There are 293 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00038 ( 0 hom., 6 hem., cov: 23)

Exomes 𝑓: 0.00054 ( 2 hom. 287 hem. )

Consequence

ZXDB
NM_007157.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.45

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021636188).

BP6

Variant X-57592280-A-C is Benign according to our data. Variant chrX-57592280-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660723.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZXDB	NM_007157.4 link	c.232A>C	p.Thr78Pro	missense_variant	Exon 1 of 1	ENST00000374888.3	NP_009088.1	P98169

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZXDB	ENST00000374888.3 link	c.232A>C	p.Thr78Pro	missense_variant	Exon 1 of 1	6	NM_007157.4	ENSP00000364023.1		P98169

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

110140

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

AN XY:

33102

show subpopulations

Gnomad AFR

AF:

0.000365

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000377

Gnomad ASJ

AF:

0.000769

Gnomad EAS

AF:

0.000590

Gnomad SAS

AF:

0.000748

Gnomad FIN

AF:

0.000170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000381

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000290

AC:

AN:

130895

Hom.:

AF XY:

0.000266

AC XY:

AN XY:

41331

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000823

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000409

Gnomad SAS exome

AF:

0.000967

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000269

Gnomad OTH exome

AF:

0.000621

GnomAD4 exome

AF:

0.000541

AC:

579

AN:

1069666

Hom.:

Cov.:

AF XY:

0.000821

AC XY:

287

AN XY:

349398

show subpopulations

Gnomad4 AFR exome

AF:

0.000462

Gnomad4 AMR exome

AF:

0.000267

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.000502

Gnomad4 SAS exome

AF:

0.00143

Gnomad4 FIN exome

AF:

0.000149

Gnomad4 NFE exome

AF:

0.000466

Gnomad4 OTH exome

AF:

0.000714

GnomAD4 genome

AF:

0.000381

AC:

AN:

110175

Hom.:

Cov.:

AF XY:

0.000181

AC XY:

AN XY:

33145

show subpopulations

Gnomad4 AFR

AF:

0.000364

Gnomad4 AMR

AF:

0.000377

Gnomad4 ASJ

AF:

0.000769

Gnomad4 EAS

AF:

0.000592

Gnomad4 SAS

AF:

0.000752

Gnomad4 FIN

AF:

0.000170

Gnomad4 NFE

AF:

0.000381

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000797

Hom.:

ExAC

AF:

0.000339

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Feb 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

ZXDB: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.042

BayesDel_addAF

Benign

-0.95

BayesDel_noAF

Benign

-1.2

CADD

Benign

0.92

DANN

Benign

0.45

DEOGEN2

Benign

0.0043

FATHMM_MKL

Benign

0.0062

LIST_S2

Benign

0.12

MetaRNN

Benign

0.0022

MetaSVM

Benign

-0.93

MutationAssessor

Benign

-2.1

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.040

REVEL

Benign

0.017

Sift

Benign

1.0

Sift4G

Benign

0.36

Polyphen

0.0

Vest4

0.016

MVP

0.043

MPC

1.3

ClinPred

0.023

GERP RS

0.49

Varity_R

0.13

gMVP

0.031

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over