rs10852936

Positions:

• chr17-39875461-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199321.3(ZPBP2):​c.889+27C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.44 in 1,505,442 control chromosomes in the GnomAD database, including 148,955 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 0.40 (12599 hom., cov: 32)
  • Exomes 𝑓: 0.44 (136356 hom.)
• Consequence: ZPBP2 NM_199321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.82

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPBP2	NM_199321.3	c.889+27C>T		intron_variant		ENST00000348931.9
ZPBP2	NM_198844.3	c.823+27C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZPBP2	ENST00000348931.9	c.889+27C>T		intron_variant		1	NM_199321.3	P1
ZPBP2	ENST00000377940.3	c.823+27C>T		intron_variant		1
ZPBP2	ENST00000583811.5	c.535+27C>T		intron_variant		3
ZPBP2	ENST00000584588.5	c.670+27C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60385 AN: 151782 Hom.: 12583 Cov.: 32

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.387

GnomAD3 exomes AF: 0.387 AC: 71195 AN: 184078 Hom.: 14146 AF XY: 0.391 AC XY: 39308 AN XY: 100452

Gnomad AFR exome AF: 0.264

Gnomad AMR exome AF: 0.307

Gnomad ASJ exome AF: 0.416

Gnomad EAS exome AF: 0.225

Gnomad SAS exome AF: 0.355

Gnomad FIN exome AF: 0.511

Gnomad NFE exome AF: 0.431

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.445 AC: 601710 AN: 1353542 Hom.: 136356 Cov.: 22 AF XY: 0.442 AC XY: 296359 AN XY: 670300

Gnomad4 AFR exome AF: 0.277

Gnomad4 AMR exome AF: 0.323

Gnomad4 ASJ exome AF: 0.419

Gnomad4 EAS exome AF: 0.255

Gnomad4 SAS exome AF: 0.356

Gnomad4 FIN exome AF: 0.512

Gnomad4 NFE exome AF: 0.465

Gnomad4 OTH exome AF: 0.418

GnomAD4 genome AF: 0.398 AC: 60439 AN: 151900 Hom.: 12599 Cov.: 32 AF XY: 0.400 AC XY: 29696 AN XY: 74188

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.417

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.386

Alfa AF: 0.436 Hom.: 19598

Bravo AF: 0.376

Asia WGS AF: 0.385 AC: 1336 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	9.9
DANN	Benign	0.79

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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

Other links and lift over

dbSNP: rs10852936; hg19: chr17-38031714; COSMIC: COSV62375084;