rs12150079

Variant names:

• chr17-39869164-G-A
• rs12150079
• NM_199321.3:c.118+550G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_199321.3(ZPBP2):​c.118+550G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.239 in 152,066 control chromosomes in the GnomAD database, including 5,240 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 0.24 (5240 hom., cov: 31)
• Consequence: ZPBP2 NM_199321.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0490
• Publications: 40 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ZPBP2	NM_199321.3	c.118+550G>A		intron_variant	Intron 2 of 7	ENST00000348931.9	NP_955353.1
ZPBP2	NM_198844.3	c.52+758G>A		intron_variant	Intron 1 of 6		NP_942141.2
ZPBP2	XM_047435318.1	c.118+550G>A		intron_variant	Intron 2 of 6		XP_047291274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ZPBP2	ENST00000348931.9	c.118+550G>A		intron_variant	Intron 2 of 7	1	NM_199321.3	ENSP00000335384.5
ZPBP2	ENST00000377940.3	c.52+758G>A		intron_variant	Intron 1 of 6	1		ENSP00000367174.3
ZPBP2	ENST00000584588.5	c.118+550G>A		intron_variant	Intron 2 of 6	5		ENSP00000462067.1
ZPBP2	ENST00000583811.5	c.52+758G>A		intron_variant	Intron 1 of 4	3		ENSP00000462463.1

Frequencies

GnomAD3 genomes AF: 0.239 AC: 36263 AN: 151948 Hom.: 5234 Cov.: 31

Gnomad AFR AF: 0.0775

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.242

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.239 AC: 36277 AN: 152066 Hom.: 5240 Cov.: 31 AF XY: 0.239 AC XY: 17738 AN XY: 74314

African (AFR) AF: 0.0774 AC: 3211 AN: 41498

American (AMR) AF: 0.252 AC: 3852 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1057 AN: 3466

East Asian (EAS) AF: 0.193 AC: 1000 AN: 5176

South Asian (SAS) AF: 0.239 AC: 1152 AN: 4824

European-Finnish (FIN) AF: 0.330 AC: 3481 AN: 10546

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21553 AN: 67966

Other (OTH) AF: 0.241 AC: 509 AN: 2112

Alfa AF: 0.291 Hom.: 22074

Bravo AF: 0.222

Asia WGS AF: 0.259 AC: 901 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.5
DANN	Benign	0.74
PhyloP100		-0.049
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: rs12150079; hg19: chr17-38025417;