Variant chr17-39871561-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_199321.3(ZPBP2):c.342G>C(p.Lys114Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000747 in 1,605,900 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000077 ( 0 hom. )

Consequence

ZPBP2
NM_199321.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.698

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41133565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
ZPBP2	NM_199321.3 linkuse as main transcript	c.342G>C	p.Lys114Asn	missense_variant	4/8	ENST00000348931.9	NP_955353.1
ZPBP2	NM_198844.3 linkuse as main transcript	c.276G>C	p.Lys92Asn	missense_variant	3/7		NP_942141.2
ZPBP2	XM_047435318.1 linkuse as main transcript	c.342G>C	p.Lys114Asn	missense_variant	4/7		XP_047291274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPBP2	ENST00000348931.9 linkuse as main transcript	c.342G>C	p.Lys114Asn	missense_variant	4/8	1	NM_199321.3	ENSP00000335384	P1	Q6X784-1
ZPBP2	ENST00000377940.3 linkuse as main transcript	c.276G>C	p.Lys92Asn	missense_variant	3/7	1		ENSP00000367174		Q6X784-2
ZPBP2	ENST00000584588.5 linkuse as main transcript	c.342G>C	p.Lys114Asn	missense_variant	4/7	5		ENSP00000462067
ZPBP2	ENST00000583811.5 linkuse as main transcript	c.53-709G>C		intron_variant		3		ENSP00000462463

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152096

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000488

AC:

AN:

246010

Hom.:

AF XY:

0.0000752

AC XY:

AN XY:

132962

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:

0.0000982

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.0000770

AC:

112

AN:

1453804

Hom.:

Cov.:

AF XY:

0.0000719

AC XY:

AN XY:

722986

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:

0.0000376

Gnomad4 NFE exome

AF:

0.0000974

Gnomad4 OTH exome

AF:

0.0000333

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152096

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000102

Hom.:

Bravo

AF:

0.0000642

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.0000247

AC:

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.342G>C (p.K114N) alteration is located in exon 4 (coding exon 4) of the ZPBP2 gene. This alteration results from a G to C substitution at nucleotide position 342, causing the lysine (K) at amino acid position 114 to be replaced by an asparagine (N). 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

Pathogenic

0.71

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.27

T;T;.

Eigen

Benign

0.17

Eigen_PC

Benign

0.033

FATHMM_MKL

Benign

0.49

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.41

T;T;T

MetaSVM

Benign

-0.77

MutationAssessor

Uncertain

2.2

M;.;.

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Uncertain

0.50

PROVEAN

Uncertain

-4.1

D;.;D

REVEL

Benign

0.17

Sift

Uncertain

0.0040

D;.;D

Sift4G

Uncertain

0.033

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.58

MutPred

0.79

Loss of methylation at K114 (P = 0.0111);Loss of methylation at K114 (P = 0.0111);.;

MVP

0.18

MPC

0.68

ClinPred

0.58

GERP RS

1.4

Varity_R

0.36

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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