rs11557467

chr17-39872381-G-T

Variant summary

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

The NM_199321.3(ZPBP2):c.518G>T(p.Ser173Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 1,612,594 control chromosomes in the GnomAD database, including 192,684 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Synonymous variant affecting the same amino acid position (i.e. S173S) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.45 (15771 hom., cov: 31)
  • Exomes 𝑓: 0.49 (176913 hom.)
• Consequence: ZPBP2 NM_199321.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.45

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 (MetaRNN=5.863309E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPBP2	NM_199321.3	c.518G>T	p.Ser173Ile	missense_variant	5/8	ENST00000348931.9
ZPBP2	NM_198844.3	c.452G>T	p.Ser151Ile	missense_variant	4/7
ZPBP2	XM_047435318.1	c.518G>T	p.Ser173Ile	missense_variant	5/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ZPBP2	ENST00000348931.9	c.518G>T	p.Ser173Ile	missense_variant	5/8	1	NM_199321.3	P1
ZPBP2	ENST00000377940.3	c.452G>T	p.Ser151Ile	missense_variant	4/7	1
ZPBP2	ENST00000583811.5	c.164G>T	p.Ser55Ile	missense_variant	2/5	3
ZPBP2	ENST00000584588.5	c.407-663G>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68470 AN: 151740 Hom.: 15751 Cov.: 31

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.420

Gnomad ASJ AF: 0.435

Gnomad EAS AF: 0.271

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.574

Gnomad MID AF: 0.377

Gnomad NFE AF: 0.494

Gnomad OTH AF: 0.433

GnomAD3 exomes AF: 0.447 AC: 112075 AN: 250718 Hom.: 26119 AF XY: 0.451 AC XY: 61083 AN XY: 135524

Gnomad AFR exome AF: 0.387

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.445

Gnomad EAS exome AF: 0.255

Gnomad SAS exome AF: 0.386

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.505

Gnomad OTH exome AF: 0.463

GnomAD4 exome AF: 0.488 AC: 713032 AN: 1460736 Hom.: 176913 Cov.: 39 AF XY: 0.485 AC XY: 352476 AN XY: 726676

Gnomad4 AFR exome AF: 0.386

Gnomad4 AMR exome AF: 0.367

Gnomad4 ASJ exome AF: 0.444

Gnomad4 EAS exome AF: 0.264

Gnomad4 SAS exome AF: 0.391

Gnomad4 FIN exome AF: 0.563

Gnomad4 NFE exome AF: 0.511

Gnomad4 OTH exome AF: 0.460

GnomAD4 genome AF: 0.451 AC: 68539 AN: 151858 Hom.: 15771 Cov.: 31 AF XY: 0.453 AC XY: 33590 AN XY: 74214

Gnomad4 AFR AF: 0.390

Gnomad4 AMR AF: 0.421

Gnomad4 ASJ AF: 0.435

Gnomad4 EAS AF: 0.271

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.574

Gnomad4 NFE AF: 0.494

Gnomad4 OTH AF: 0.432

Alfa AF: 0.482 Hom.: 37282

Bravo AF: 0.430

TwinsUK AF: 0.508 AC: 1883

ALSPAC AF: 0.512 AC: 1974

ESP6500AA AF: 0.326 AC: 1437

ESP6500EA AF: 0.487 AC: 4192

ExAC AF: 0.445 AC: 54080

Asia WGS AF: 0.394 AC: 1367 AN: 3468

EpiCase AF: 0.491

EpiControl AF: 0.484

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.56	T
BayesDel_noAF	Benign	-0.43
Cadd	Benign	21
Dann	Benign	0.91
DEOGEN2	Benign	0.17	T;.;.
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.31
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.27	T;T;T
MetaRNN	Benign	0.00059	T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N;.;.
MutationTaster	Benign	1.0	P;P;P
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.9	D;.;D
REVEL	Benign	0.096
Sift	Benign	0.041	D;.;D
Sift4G	Uncertain	0.0050	D;T;D
Polyphen		0.29	B;.;B
Vest4		0.064
MPC		0.23
ClinPred		0.0086	T
GERP RS		4.4
Varity_R		0.14
gMVP		0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs11557467; hg19: chr17-38028634; COSMIC: COSV62375604;