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GeneBe

7-50081796-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BS1BS2

The NM_007009.3(ZPBP):c.312G>A(p.Gly104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000833 in 1,611,294 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0045 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00045 ( 3 hom. )

Consequence

ZPBP
NM_007009.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.00300
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.43).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-50081796-C-T is Benign according to our data. Variant chr7-50081796-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3039398.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.003 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00455 (691/151982) while in subpopulation AFR AF= 0.0162 (671/41508). AF 95% confidence interval is 0.0152. There are 2 homozygotes in gnomad4. There are 324 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZPBPNM_007009.3 linkuse as main transcriptc.312G>A p.Gly104= synonymous_variant 3/8 ENST00000046087.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZPBPENST00000046087.7 linkuse as main transcriptc.312G>A p.Gly104= synonymous_variant 3/81 NM_007009.3 P4Q9BS86-1
ZPBPENST00000419417.5 linkuse as main transcriptc.312G>A p.Gly104= synonymous_variant 3/81 A2Q9BS86-2
ZPBPENST00000450231.1 linkuse as main transcriptc.195G>A p.Gly65= synonymous_variant 5/53

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00455
AC:
691
AN:
151864
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0162
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000788
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000295
Gnomad OTH
AF:
0.00288
GnomAD3 exomes
AF:
0.00114
AC:
285
AN:
250312
Hom.:
2
AF XY:
0.000872
AC XY:
118
AN XY:
135294
show subpopulations
Gnomad AFR exome
AF:
0.0154
Gnomad AMR exome
AF:
0.000902
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000885
Gnomad OTH exome
AF:
0.000492
GnomAD4 exome
AF:
0.000447
AC:
652
AN:
1459312
Hom.:
3
Cov.:
31
AF XY:
0.000368
AC XY:
267
AN XY:
725978
show subpopulations
Gnomad4 AFR exome
AF:
0.0159
Gnomad4 AMR exome
AF:
0.00110
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000171
Gnomad4 OTH exome
AF:
0.000864
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00455
AC:
691
AN:
151982
Hom.:
2
Cov.:
33
AF XY:
0.00436
AC XY:
324
AN XY:
74308
show subpopulations
Gnomad4 AFR
AF:
0.0162
Gnomad4 AMR
AF:
0.000787
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000295
Gnomad4 OTH
AF:
0.00285
Alfa
AF:
0.00211
Hom.:
2
Bravo
AF:
0.00519
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.000109
EpiControl
AF:
0.00

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 submitterclinical testingPreventionGenetics, part of Exact SciencesMar 25, 2019This 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
-0.43
Cadd
Benign
5.7
Dann
Benign
0.53

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

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

Other links and lift over

dbSNP: rs79915261; hg19: chr7-50121392; API