Variant 7-50058132-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_007009.3(ZPBP):c.344G>A(p.Arg115His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000296 in 1,613,572 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 4 hom. )

Consequence

ZPBP
NM_007009.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.470

Variant links:

Genes affected

ZPBP (HGNC:15662): (zona pellucida binding protein) ZPBP is one of several proteins that are thought to participate in secondary binding between acrosome-reacted sperm and the egg-specific extracellular matrix, the zona pellucida (McLeskey et al., 1998 [PubMed 9378618]).[supplied by OMIM, Aug 2008]

ZPBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.019204438).

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPBP	NM_007009.3 linkuse as main transcript	c.344G>A	p.Arg115His	missense_variant	4/8	ENST00000046087.7	NP_008940.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPBP	ENST00000046087.7 linkuse as main transcript	c.344G>A	p.Arg115His	missense_variant	4/8	1	NM_007009.3	ENSP00000046087	P4	Q9BS86-1
ZPBP	ENST00000419417.5 linkuse as main transcript	c.341G>A	p.Arg114His	missense_variant	4/8	1		ENSP00000402071	A2	Q9BS86-2

Frequencies

GnomAD3 genomes

AF:

0.000263

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.000622

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000470

AC:

118

AN:

251176

Hom.:

AF XY:

0.000486

AC XY:

AN XY:

135750

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.00101

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000490

Gnomad SAS exome

AF:

0.000751

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000335

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.000299

AC:

437

AN:

1461352

Hom.:

Cov.:

AF XY:

0.000319

AC XY:

232

AN XY:

726958

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000858

Gnomad4 FIN exome

AF:

0.0000937

Gnomad4 NFE exome

AF:

0.000246

Gnomad4 OTH exome

AF:

0.000381

GnomAD4 genome

AF:

0.000263

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000393

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000578

Gnomad4 SAS

AF:

0.000623

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000296

Hom.:

Bravo

AF:

0.000280

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000503

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000600

EpiControl

AF:

0.000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 09, 2021

The c.344G>A (p.R115H) alteration is located in exon 4 (coding exon 4) of the ZPBP gene. This alteration results from a G to A substitution at nucleotide position 344, causing the arginine (R) at amino acid position 115 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.065

T;.

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.079

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.27

PROVEAN

Benign

0.10

N;N

REVEL

Benign

0.12

Sift

Benign

0.49

T;D

Sift4G

Uncertain

0.018

D;D

Polyphen

0.19

B;.

Vest4

0.13

MVP

0.68

MPC

0.22

ClinPred

0.015

GERP RS

0.30

Varity_R

0.026

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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