Variant chr17-39875395-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_199321.3(ZPBP2):c.850A>G(p.Lys284Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00295 in 1,613,640 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 12 hom. )

Consequence

ZPBP2
NM_199321.3 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.68

Variant links:

Genes affected

ZPBP2 (HGNC:20678): (zona pellucida binding protein 2) Predicted to be involved in acrosome assembly and binding activity of sperm to zona pellucida. Predicted to act upstream of or within membrane lipid metabolic process and regulation of gene expression. Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ZPBP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.018212825).

BP6

Variant 17-39875395-A-G is Benign according to our data. Variant chr17-39875395-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 719398.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPBP2	NM_199321.3 linkuse as main transcript	c.850A>G	p.Lys284Glu	missense_variant	7/8	ENST00000348931.9	NP_955353.1	Q6X784-1
ZPBP2	NM_198844.3 linkuse as main transcript	c.784A>G	p.Lys262Glu	missense_variant	6/7		NP_942141.2	Q6X784-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZPBP2	ENST00000348931.9 linkuse as main transcript	c.850A>G	p.Lys284Glu	missense_variant	7/8	1	NM_199321.3	ENSP00000335384.5	Q6X784-1
ZPBP2	ENST00000377940.3 linkuse as main transcript	c.784A>G	p.Lys262Glu	missense_variant	6/7	1		ENSP00000367174.3	Q6X784-2
ZPBP2	ENST00000584588.5 linkuse as main transcript	c.631A>G	p.Lys211Glu	missense_variant	6/7	5		ENSP00000462067.1	J3KRM0
ZPBP2	ENST00000583811.5 linkuse as main transcript	c.496A>G	p.Lys166Glu	missense_variant	4/5	3		ENSP00000462463.1	J3KSF6

Frequencies

GnomAD3 genomes

AF:

0.00215

AC:

327

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000982

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00687

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00301

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00233

AC:

583

AN:

250632

Hom.:

AF XY:

0.00224

AC XY:

304

AN XY:

135466

show subpopulations

Gnomad AFR exome

AF:

0.000554

Gnomad AMR exome

AF:

0.000817

Gnomad ASJ exome

AF:

0.000596

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000987

Gnomad FIN exome

AF:

0.00795

Gnomad NFE exome

AF:

0.00304

Gnomad OTH exome

AF:

0.00327

GnomAD4 exome

AF:

0.00303

AC:

4428

AN:

1461340

Hom.:

Cov.:

AF XY:

0.00291

AC XY:

2112

AN XY:

726952

show subpopulations

Gnomad4 AFR exome

AF:

0.000628

Gnomad4 AMR exome

AF:

0.000740

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000813

Gnomad4 FIN exome

AF:

0.00902

Gnomad4 NFE exome

AF:

0.00336

Gnomad4 OTH exome

AF:

0.00242

GnomAD4 genome

AF:

0.00215

AC:

327

AN:

152300

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.000981

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00687

Gnomad4 NFE

AF:

0.00301

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00279

Hom.:

Bravo

AF:

0.00170

TwinsUK

AF:

0.00351

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.00236

AC:

286

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00285

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 15, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Pathogenic

DANN

Benign

0.97

DEOGEN2

Benign

0.20

T;.;T;.

Eigen

Uncertain

0.59

Eigen_PC

Uncertain

0.56

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.87

D;D;D;D

M_CAP

Benign

0.079

MetaRNN

Benign

0.018

T;T;T;T

MetaSVM

Uncertain

0.098

MutationAssessor

Benign

2.0

M;.;.;.

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.2

N;.;.;N

REVEL

Benign

0.26

Sift

Benign

0.17

T;.;.;T

Sift4G

Uncertain

0.013

D;D;D;D

Polyphen

1.0

D;.;.;D

Vest4

0.71

MVP

0.52

MPC

0.74

ClinPred

0.027

GERP RS

5.7

Varity_R

0.23

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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