rs10852936

Variant names:

• chr17-39875461-C-T
• rs10852936
• NM_199321.3:c.889+27C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 47 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
ZPBP2	NM_199321.3	c.889+27C>T		intron_variant	Intron 7 of 7	ENST00000348931.9	NP_955353.1
ZPBP2	NM_198844.3	c.823+27C>T		intron_variant	Intron 6 of 6		NP_942141.2
ZPBP2	XM_047435318.1	c.*192C>T		downstream_gene_variant			XP_047291274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZPBP2	ENST00000348931.9	c.889+27C>T		intron_variant	Intron 7 of 7	1	NM_199321.3	ENSP00000335384.5
ZPBP2	ENST00000377940.3	c.823+27C>T		intron_variant	Intron 6 of 6	1		ENSP00000367174.3
ZPBP2	ENST00000584588.5	c.670+27C>T		intron_variant	Intron 6 of 6	5		ENSP00000462067.1
ZPBP2	ENST00000583811.5	c.535+27C>T		intron_variant	Intron 4 of 4	3		ENSP00000462463.1

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

GnomAD2 exomes AF: 0.387 AC: 71195 AN: 184078 AF XY: 0.391

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 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

African (AFR) AF: 0.277 AC: 8210 AN: 29588

American (AMR) AF: 0.323 AC: 10582 AN: 32770

Ashkenazi Jewish (ASJ) AF: 0.419 AC: 9767 AN: 23296

East Asian (EAS) AF: 0.255 AC: 9474 AN: 37140

South Asian (SAS) AF: 0.356 AC: 24694 AN: 69346

European-Finnish (FIN) AF: 0.512 AC: 25285 AN: 49364

Middle Eastern (MID) AF: 0.390 AC: 2111 AN: 5410

European-Non Finnish (NFE) AF: 0.465 AC: 488265 AN: 1050848

Other (OTH) AF: 0.418 AC: 23322 AN: 55780

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

African (AFR) AF: 0.290 AC: 11999 AN: 41410

American (AMR) AF: 0.393 AC: 6000 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1444 AN: 3466

East Asian (EAS) AF: 0.270 AC: 1398 AN: 5180

South Asian (SAS) AF: 0.372 AC: 1789 AN: 4814

European-Finnish (FIN) AF: 0.532 AC: 5592 AN: 10502

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.452 AC: 30696 AN: 67942

Other (OTH) AF: 0.386 AC: 816 AN: 2112

Alfa AF: 0.428 Hom.: 32252

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
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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