Variant rs11557467 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_199321.3(ZPBP2):c.518G>T(p.Ser173Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,612,594 control chromosomes in the GnomAD database, including 192,684 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.45 ( 15771 hom., cov: 31)

Exomes 𝑓: 0.49 ( 176913 hom. )

Consequence

ZPBP2
NM_199321.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=5.863309E-4).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPBP2	NM_199321.3 link	c.518G>T	p.Ser173Ile	missense_variant	5/8	ENST00000348931.9	NP_955353.1	Q6X784-1
ZPBP2	NM_198844.3 link	c.452G>T	p.Ser151Ile	missense_variant	4/7		NP_942141.2	Q6X784-2
ZPBP2	XM_047435318.1 link	c.518G>T	p.Ser173Ile	missense_variant	5/7		XP_047291274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ZPBP2	ENST00000348931.9 link	c.518G>T	p.Ser173Ile	missense_variant	5/8	1	NM_199321.3	ENSP00000335384.5	Q6X784-1
ZPBP2	ENST00000377940.3 link	c.452G>T	p.Ser151Ile	missense_variant	4/7	1		ENSP00000367174.3	Q6X784-2
ZPBP2	ENST00000583811.5 link	c.164G>T	p.Ser55Ile	missense_variant	2/5	3		ENSP00000462463.1	J3KSF6
ZPBP2	ENST00000584588.5 link	c.407-663G>T		intron_variant		5		ENSP00000462067.1	J3KRM0

Frequencies

GnomAD3 genomes

AF:

0.451

AC:

68470

AN:

151740

Hom.:

15751

Cov.:

show subpopulations

Gnomad AFR

AF:

0.390

Gnomad AMI

AF:

0.670

Gnomad AMR

AF:

0.420

Gnomad ASJ

AF:

0.435

Gnomad EAS

AF:

0.271

Gnomad SAS

AF:

0.389

Gnomad FIN

AF:

0.574

Gnomad MID

AF:

0.377

Gnomad NFE

AF:

0.494

Gnomad OTH

AF:

0.433

GnomAD3 exomes

AF:

0.447

AC:

112075

AN:

250718

Hom.:

26119

AF XY:

0.451

AC XY:

61083

AN XY:

135524

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.360

Gnomad ASJ exome

AF:

0.445

Gnomad EAS exome

AF:

0.255

Gnomad SAS exome

AF:

0.386

Gnomad FIN exome

AF:

0.573

Gnomad NFE exome

AF:

0.505

Gnomad OTH exome

AF:

0.463

GnomAD4 exome

AF:

0.488

AC:

713032

AN:

1460736

Hom.:

176913

Cov.:

AF XY:

0.485

AC XY:

352476

AN XY:

726676

show subpopulations

Gnomad4 AFR exome

AF:

0.386

Gnomad4 AMR exome

AF:

0.367

Gnomad4 ASJ exome

AF:

0.444

Gnomad4 EAS exome

AF:

0.264

Gnomad4 SAS exome

AF:

0.391

Gnomad4 FIN exome

AF:

0.563

Gnomad4 NFE exome

AF:

0.511

Gnomad4 OTH exome

AF:

0.460

GnomAD4 genome

AF:

0.451

AC:

68539

AN:

151858

Hom.:

15771

Cov.:

AF XY:

0.453

AC XY:

33590

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.390

Gnomad4 AMR

AF:

0.421

Gnomad4 ASJ

AF:

0.435

Gnomad4 EAS

AF:

0.271

Gnomad4 SAS

AF:

0.389

Gnomad4 FIN

AF:

0.574

Gnomad4 NFE

AF:

0.494

Gnomad4 OTH

AF:

0.432

Alfa

AF:

0.482

Hom.:

37282

Bravo

AF:

0.430

TwinsUK

AF:

0.508

AC:

1883

ALSPAC

AF:

0.512

AC:

1974

ESP6500AA

AF:

0.326

AC:

1437

ESP6500EA

AF:

0.487

AC:

4192

ExAC

AF:

0.445

AC:

54080

Asia WGS

AF:

0.394

AC:

1367

AN:

3468

EpiCase

AF:

0.491

EpiControl

AF:

0.484

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.51

LIST_S2

Benign

0.27

T;T;T

MetaRNN

Benign

0.00059

T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.34

N;.;.

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.9

D;.;D

REVEL

Benign

0.096

Sift

Benign

0.041

D;.;D

Sift4G

Uncertain

0.0050

D;T;D

Polyphen

0.29

B;.;B

Vest4

0.064

MPC

0.23

ClinPred

0.0086

GERP RS

4.4

Varity_R

0.14

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over