Genetic Variant ZPBP2:p.Leu7Leu (chr17-39868373-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_199321.3(ZPBP2):c.19C>T(p.Leu7Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.437 in 1,609,322 control chromosomes in the GnomAD database, including 159,583 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.36 ( 11199 hom., cov: 31)

Exomes 𝑓: 0.45 ( 148384 hom. )

Consequence

ZPBP2
NM_199321.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.16

Publications

48 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:

ENSG00000302760 (HGNC:):

ENSG00000302760 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPBP2	NM_199321.3 link	c.19C>T	p.Leu7Leu	synonymous_variant	Exon 1 of 8	ENST00000348931.9	NP_955353.1	Q6X784-1
ZPBP2	NM_198844.3 link	c.19C>T	p.Leu7Leu	synonymous_variant	Exon 1 of 7		NP_942141.2	Q6X784-2
ZPBP2	XM_047435318.1 link	c.19C>T	p.Leu7Leu	synonymous_variant	Exon 1 of 7		XP_047291274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZPBP2	ENST00000348931.9 link	c.19C>T	p.Leu7Leu	synonymous_variant	Exon 1 of 8	1	NM_199321.3	ENSP00000335384.5		Q6X784-1

Frequencies

GnomAD3 genomes

AF:

0.357

AC:

54275

AN:

151848

Hom.:

11187

Cov.:

show subpopulations

Gnomad AFR

AF:

0.150

Gnomad AMI

AF:

0.662

Gnomad AMR

AF:

0.378

Gnomad ASJ

AF:

0.417

Gnomad EAS

AF:

0.268

Gnomad SAS

AF:

0.370

Gnomad FIN

AF:

0.531

Gnomad MID

AF:

0.358

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.356

GnomAD2 exomes

AF:

0.400

AC:

99175

AN:

248108

AF XY:

0.408

show subpopulations

Gnomad AFR exome

AF:

0.142

Gnomad AMR exome

AF:

0.329

Gnomad ASJ exome

AF:

0.429

Gnomad EAS exome

AF:

0.254

Gnomad FIN exome

AF:

0.531

Gnomad NFE exome

AF:

0.465

Gnomad OTH exome

AF:

0.428

GnomAD4 exome

AF:

0.446

AC:

649348

AN:

1457356

Hom.:

148384

Cov.:

AF XY:

0.444

AC XY:

321949

AN XY:

725236

show subpopulations

African (AFR)

AF:

0.140

AC:

4694

AN:

33476

American (AMR)

AF:

0.335

AC:

14961

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

11125

AN:

26124

East Asian (EAS)

AF:

0.264

AC:

10462

AN:

39684

South Asian (SAS)

AF:

0.372

AC:

32077

AN:

86236

European-Finnish (FIN)

AF:

0.518

AC:

25513

AN:

49212

Middle Eastern (MID)

AF:

0.392

AC:

2243

AN:

5718

European-Non Finnish (NFE)

AF:

0.471

AC:

523133

AN:

1111840

Other (OTH)

AF:

0.417

AC:

25140

AN:

60350

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

20846

41692

62537

83383

104229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15330

30660

45990

61320

76650

<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:

0.357

AC:

54314

AN:

151966

Hom.:

11199

Cov.:

AF XY:

0.361

AC XY:

26803

AN XY:

74264

show subpopulations

African (AFR)

AF:

0.150

AC:

6233

AN:

41474

American (AMR)

AF:

0.379

AC:

5796

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.417

AC:

1445

AN:

3468

East Asian (EAS)

AF:

0.268

AC:

1377

AN:

5134

South Asian (SAS)

AF:

0.371

AC:

1789

AN:

4824

European-Finnish (FIN)

AF:

0.531

AC:

5603

AN:

10556

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.451

AC:

30623

AN:

67918

Other (OTH)

AF:

0.354

AC:

747

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1611

3222

4833

6444

8055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

522

1044

1566

2088

2610

<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:

0.374

Hom.:

8288

Bravo

AF:

0.331

Asia WGS

AF:

0.365

AC:

1267

AN:

3478

EpiCase

AF:

0.455

EpiControl

AF:

0.449

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.77

PhyloP100

1.2

PromoterAI

0.031

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over