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

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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	UniProt
ZPBP2	ENST00000348931.9 link	c.19C>T	p.Leu7Leu	synonymous_variant	Exon 1 of 8	1	NM_199321.3	ENSP00000335384.5	Q6X784-1
ZPBP2	ENST00000377940.3 link	c.19C>T	p.Leu7Leu	synonymous_variant	Exon 1 of 7	1		ENSP00000367174.3	Q6X784-2
ZPBP2	ENST00000584588.5 link	c.19C>T	p.Leu7Leu	synonymous_variant	Exon 1 of 7	5		ENSP00000462067.1	J3KRM0
ZPBP2	ENST00000583811.5 link	c.19C>T	p.Leu7Leu	synonymous_variant	Exon 1 of 5	3		ENSP00000462463.1	J3KSF6

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

GnomAD3 exomes

AF:

0.400

AC:

99175

AN:

248108

Hom.:

21191

AF XY:

0.408

AC XY:

54889

AN XY:

134478

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 SAS exome

AF:

0.367

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

Gnomad4 AFR exome

AF:

0.140

Gnomad4 AMR exome

AF:

0.335

Gnomad4 ASJ exome

AF:

0.426

Gnomad4 EAS exome

AF:

0.264

Gnomad4 SAS exome

AF:

0.372

Gnomad4 FIN exome

AF:

0.518

Gnomad4 NFE exome

AF:

0.471

Gnomad4 OTH exome

AF:

0.417

GnomAD4 genome

AF:

0.357

AC:

54314

AN:

151966

Hom.:

11199

Cov.:

AF XY:

0.361

AC XY:

26803

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.150

Gnomad4 AMR

AF:

0.379

Gnomad4 ASJ

AF:

0.417

Gnomad4 EAS

AF:

0.268

Gnomad4 SAS

AF:

0.371

Gnomad4 FIN

AF:

0.531

Gnomad4 NFE

AF:

0.451

Gnomad4 OTH

AF:

0.354

Alfa

AF:

0.409

Hom.:

7110

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

DANN

Benign

0.77

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

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over