rs1019096

Positions:

• chr7-76417007-A-G
• chr7-76417007-A-T

Variant summary

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

The ENST00000336517.8(ZP3):​c.-66-8045A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 145,392 control chromosomes in the GnomAD database, including 26,559 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 0.59 (26559 hom., cov: 24)
• Consequence: ZP3 ENST00000336517.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.765

Genes affected

ZP3 (HGNC:13189): (zona pellucida glycoprotein 3) The zona pellucida is an extracellular matrix that surrounds the oocyte and early embryo. It is composed primarily of three or four glycoproteins with various functions during fertilization and preimplantation development. The protein encoded by this gene is a structural component of the zona pellucida and functions in primary binding and induction of the sperm acrosome reaction. The nascent protein contains a N-terminal signal peptide sequence, a conserved ZP domain, a C-terminal consensus furin cleavage site, and a transmembrane domain. It is hypothesized that furin cleavage results in release of the mature protein from the plasma membrane for subsequent incorporation into the zona pellucida matrix. However, the requirement for furin cleavage in this process remains controversial based on mouse studies. A variation in the last exon of this gene has previously served as the basis for an additional ZP3 locus; however, sequence and literature review reveals that there is only one full-length ZP3 locus in the human genome. Another locus encoding a bipartite transcript designated POMZP3 contains a duplication of the last four exons of ZP3, including the above described variation, and maps closely to this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ZP3	NM_007155.6	c.-66-8045A>G		intron_variant			NP_009086.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZP3	ENST00000336517.8	c.-66-8045A>G		intron_variant		1		ENSP00000337310

Frequencies

GnomAD3 genomes AF: 0.592 AC: 86045 AN: 145366 Hom.: 26533 Cov.: 24

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.483

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.648

Gnomad EAS AF: 0.557

Gnomad SAS AF: 0.629

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.654

Gnomad NFE AF: 0.529

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.592 AC: 86082 AN: 145392 Hom.: 26559 Cov.: 24 AF XY: 0.586 AC XY: 41395 AN XY: 70600

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.549

Gnomad4 ASJ AF: 0.648

Gnomad4 EAS AF: 0.556

Gnomad4 SAS AF: 0.630

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.529

Gnomad4 OTH AF: 0.586

Alfa AF: 0.557 Hom.: 19323

Bravo AF: 0.609

Asia WGS AF: 0.529 AC: 1689 AN: 3200

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.41
DANN	Benign	0.43

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1019096; hg19: chr7-76046324;