dbSNP rs779439070: ZPBP2:p.Pro185Ser (chr17-39872416-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_199321.3(ZPBP2):c.553C>T(p.Pro185Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000105 in 1,613,238 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

ZPBP2
NM_199321.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.27

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.116163045).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPBP2	NM_199321.3	MANE Select	c.553C>T	p.Pro185Ser	missense	Exon 5 of 8	NP_955353.1	Q6X784-1
	ZPBP2	NM_198844.3		c.487C>T	p.Pro163Ser	missense	Exon 4 of 7	NP_942141.2	Q6X784-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ZPBP2	ENST00000348931.9	TSL:1 MANE Select	c.553C>T	p.Pro185Ser	missense	Exon 5 of 8	ENSP00000335384.5	Q6X784-1
ZPBP2	ENST00000377940.3	TSL:1	c.487C>T	p.Pro163Ser	missense	Exon 4 of 7	ENSP00000367174.3	Q6X784-2
ZPBP2	ENST00000583811.5	TSL:3	c.199C>T	p.Pro67Ser	missense	Exon 2 of 5	ENSP00000462463.1	J3KSF6

Frequencies

GnomAD3 genomes

AF:

0.000132

AC:

AN:

152072

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:

0.000279

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000438

AC:

AN:

250930

AF XY:

0.0000442

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000881

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000102

AC:

149

AN:

1461166

Hom.:

Cov.:

AF XY:

0.0000880

AC XY:

AN XY:

726924

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33456

American (AMR)

AF:

0.00

AC:

AN:

44700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39598

South Asian (SAS)

AF:

0.00

AC:

AN:

86210

European-Finnish (FIN)

AF:

0.0000376

AC:

AN:

53190

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.000122

AC:

136

AN:

1111778

Other (OTH)

AF:

0.000182

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000132

AC:

AN:

152072

Hom.:

Cov.:

AF XY:

0.0000808

AC XY:

AN XY:

74268

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41416

American (AMR)

AF:

0.00

AC:

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5196

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10580

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000279

AC:

AN:

68008

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000389

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.84

DEOGEN2

Benign

0.030

Eigen

Benign

-0.059

Eigen_PC

Benign

0.0099

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.77

M_CAP

Benign

0.017

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.3

PhyloP100

1.3

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.2

REVEL

Benign

0.061

Sift

Benign

0.13

Sift4G

Benign

0.40

Polyphen

0.44

Vest4

0.20

MVP

0.26

MPC

0.20

ClinPred

0.067

GERP RS

3.5

Varity_R

0.040

gMVP

0.54

Mutation Taster

=87/13

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over