Variant 7-50031319-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_007009.3(ZPBP):c.488-9T>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000611 in 1,602,960 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00063 ( 3 hom. )

Consequence

ZPBP
NM_007009.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.2900

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0200

Variant links:

Genes affected

ZPBP (HGNC:15662): (zona pellucida binding protein) ZPBP is one of several proteins that are thought to participate in secondary binding between acrosome-reacted sperm and the egg-specific extracellular matrix, the zona pellucida (McLeskey et al., 1998 [PubMed 9378618]).[supplied by OMIM, Aug 2008]

ZPBP links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 7-50031319-A-C is Benign according to our data. Variant chr7-50031319-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3046187.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ZPBP	NM_007009.3 linkuse as main transcript	c.488-9T>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000046087.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
ZPBP	ENST00000046087.7 linkuse as main transcript	c.488-9T>G	splice_polypyrimidine_tract_variant, intron_variant	1	NM_007009.3	P4	Q9BS86-1
ZPBP	ENST00000419417.5 linkuse as main transcript	c.485-9T>G	splice_polypyrimidine_tract_variant, intron_variant	1		A2	Q9BS86-2
ZPBP	ENST00000491129.5 linkuse as main transcript	n.240+24866T>G	intron_variant, non_coding_transcript_variant	3

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000279

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.00116

AC:

276

AN:

237250

Hom.:

AF XY:

0.00139

AC XY:

180

AN XY:

129166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000480

Gnomad ASJ exome

AF:

0.00483

Gnomad EAS exome

AF:

0.000115

Gnomad SAS exome

AF:

0.00549

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000433

Gnomad OTH exome

AF:

0.00103

GnomAD4 exome

AF:

0.000627

AC:

909

AN:

1450614

Hom.:

Cov.:

AF XY:

0.000760

AC XY:

548

AN XY:

721274

show subpopulations

Gnomad4 AFR exome

AF:

0.0000906

Gnomad4 AMR exome

AF:

0.000478

Gnomad4 ASJ exome

AF:

0.00496

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00503

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000243

Gnomad4 OTH exome

AF:

0.000818

GnomAD4 genome

AF:

0.000459

AC:

AN:

152346

Hom.:

Cov.:

AF XY:

0.000510

AC XY:

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00432

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000279

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000609

Hom.:

Bravo

AF:

0.000363

Asia WGS

AF:

0.00289

AC:

AN:

3474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

ZPBP-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.29

dbscSNV1_RF

Benign

0.40

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over