rs11557467

Variant names:

• chr17-39872381-G-T
• rs11557467
• NM_199321.3:c.518G>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.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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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
• Publications: 106 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 (MetaRNN=5.863309E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.489 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_199321.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPBP2	NM_199321.3	MANE Select	c.518G>T	p.Ser173Ile	missense	Exon 5 of 8	NP_955353.1	Q6X784-1
	ZPBP2	NM_198844.3		c.452G>T	p.Ser151Ile	missense	Exon 4 of 7	NP_942141.2	Q6X784-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZPBP2	ENST00000348931.9	TSL:1 MANE Select	c.518G>T	p.Ser173Ile	missense	Exon 5 of 8	ENSP00000335384.5	Q6X784-1
	ZPBP2	ENST00000377940.3	TSL:1	c.452G>T	p.Ser151Ile	missense	Exon 4 of 7	ENSP00000367174.3	Q6X784-2
	ZPBP2	ENST00000583811.5	TSL:3	c.164G>T	p.Ser55Ile	missense	Exon 2 of 5	ENSP00000462463.1	J3KSF6

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

GnomAD2 exomes AF: 0.447 AC: 112075 AN: 250718 AF XY: 0.451

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 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

African (AFR) AF: 0.386 AC: 12911 AN: 33434

American (AMR) AF: 0.367 AC: 16397 AN: 44648

Ashkenazi Jewish (ASJ) AF: 0.444 AC: 11584 AN: 26108

East Asian (EAS) AF: 0.264 AC: 10448 AN: 39556

South Asian (SAS) AF: 0.391 AC: 33668 AN: 86128

European-Finnish (FIN) AF: 0.563 AC: 29965 AN: 53250

Middle Eastern (MID) AF: 0.415 AC: 2386 AN: 5748

European-Non Finnish (NFE) AF: 0.511 AC: 567897 AN: 1111524

Other (OTH) AF: 0.460 AC: 27776 AN: 60340

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

African (AFR) AF: 0.390 AC: 16160 AN: 41430

American (AMR) AF: 0.421 AC: 6420 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.435 AC: 1506 AN: 3464

East Asian (EAS) AF: 0.271 AC: 1399 AN: 5162

South Asian (SAS) AF: 0.389 AC: 1877 AN: 4820

European-Finnish (FIN) AF: 0.574 AC: 6035 AN: 10520

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.494 AC: 33512 AN: 67896

Other (OTH) AF: 0.432 AC: 911 AN: 2108

Alfa AF: 0.476 Hom.: 47438

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 v4.9

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
MetaRNN	Benign	0.00059	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.34	N
PhyloP100		2.5
PrimateAI	Benign	0.43	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.096
Sift	Benign	0.041	D
Sift4G	Uncertain	0.0050	D
Polyphen		0.29	B
Vest4		0.064
MPC		0.23
ClinPred		0.0086	T
GERP RS		4.4
Varity_R		0.14
gMVP		0.53
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11557467; hg19: chr17-38028634; COSMIC: COSV62375604;