Variant chr7-49983410-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_007009.3(ZPBP):c.893G>C(p.Trp298Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,613,196 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000035 ( 2 hom. )

Consequence

ZPBP
NM_007009.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.42

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 Likely_benign. Variant got -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.79

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZPBP	NM_007009.3 linkuse as main transcript	c.893G>C	p.Trp298Ser	missense_variant	7/8	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.893G>C	p.Trp298Ser	missense_variant	7/8	1	NM_007009.3	ENSP00000046087	P4	Q9BS86-1
ZPBP	ENST00000419417.5 linkuse as main transcript	c.890G>C	p.Trp297Ser	missense_variant	7/8	1		ENSP00000402071	A2	Q9BS86-2
ZPBP	ENST00000491129.5 linkuse as main transcript	n.350G>C		non_coding_transcript_exon_variant	2/4	3

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151918

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251250

Hom.:

AF XY:

0.0000368

AC XY:

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000349

AC:

AN:

1461278

Hom.:

Cov.:

AF XY:

0.0000426

AC XY:

AN XY:

726954

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000459

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

151918

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.0000189

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Apr 15, 2024

The c.893G>C (p.W298S) alteration is located in exon 7 (coding exon 7) of the ZPBP gene. This alteration results from a G to C substitution at nucleotide position 893, causing the tryptophan (W) at amino acid position 298 to be replaced by a serine (S). 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

Uncertain

0.52

BayesDel_addAF

Benign

-0.056

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.32

T;.

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.66

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.64

T;T

M_CAP

Benign

0.013

MetaRNN

Pathogenic

0.79

D;D

MetaSVM

Benign

-0.70

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-4.2

D;D

REVEL

Uncertain

0.31

Sift

Benign

0.45

T;T

Sift4G

Benign

0.16

T;T

Polyphen

0.99

D;.

Vest4

0.69

MVP

0.84

MPC

0.90

ClinPred

0.91

GERP RS

5.8

Varity_R

0.49

gMVP

0.69

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