rs1054609

Positions:

• chr17-39877024-A-C
• chr17-39877024-A-G

Variant summary

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

The NM_199321.3(ZPBP2):​c.*215A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 444,314 control chromosomes in the GnomAD database, including 40,698 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 (12605 hom., cov: 31)
  • Exomes 𝑓: 0.43 (28093 hom.)
• Consequence: ZPBP2 NM_199321.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.35

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 (BayesDel_noAF=-0.82).
• 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/exons	MANE	Protein	UniProt
ZPBP2	NM_199321.3	c.*215A>C		3_prime_UTR_variant	8/8	ENST00000348931.9	NP_955353.1
ZPBP2	NM_198844.3	c.*215A>C		3_prime_UTR_variant	7/7		NP_942141.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ZPBP2	ENST00000348931.9	c.*215A>C		3_prime_UTR_variant	8/8	1	NM_199321.3	ENSP00000335384.5
ZPBP2	ENST00000377940.3	c.*215A>C		3_prime_UTR_variant	7/7	1		ENSP00000367174.3
ZPBP2	ENST00000584588.5	c.*215A>C		3_prime_UTR_variant	7/7	5		ENSP00000462067.1

Frequencies

GnomAD3 genomes AF: 0.398 AC: 60410 AN: 151872 Hom.: 12589 Cov.: 31

Gnomad AFR AF: 0.290

Gnomad AMI AF: 0.659

Gnomad AMR AF: 0.392

Gnomad ASJ AF: 0.415

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.532

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.433 AC: 126517 AN: 292324 Hom.: 28093 Cov.: 5 AF XY: 0.428 AC XY: 66194 AN XY: 154480

Gnomad4 AFR exome AF: 0.301

Gnomad4 AMR exome AF: 0.357

Gnomad4 ASJ exome AF: 0.426

Gnomad4 EAS exome AF: 0.268

Gnomad4 SAS exome AF: 0.365

Gnomad4 FIN exome AF: 0.519

Gnomad4 NFE exome AF: 0.466

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.398 AC: 60464 AN: 151990 Hom.: 12605 Cov.: 31 AF XY: 0.400 AC XY: 29706 AN XY: 74254

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.393

Gnomad4 ASJ AF: 0.415

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.532

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.387

Alfa AF: 0.429 Hom.: 3727

Bravo AF: 0.376

Asia WGS AF: 0.386 AC: 1339 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	10
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs1054609; hg19: chr17-38033277;