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7-50031300-C-T

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_007009.3(ZPBP):c.498G>A(p.Glu166=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000166 in 1,609,574 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00068 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

ZPBP
NM_007009.3 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.143
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 Likely_benign. Variant got -5 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
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=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 7-50031300-C-T is Benign according to our data. Variant chr7-50031300-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3044696.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=-0.143 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
ZPBPNM_007009.3 linkuse as main transcriptc.498G>A p.Glu166= synonymous_variant 5/8 ENST00000046087.7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
ZPBPENST00000046087.7 linkuse as main transcriptc.498G>A p.Glu166= synonymous_variant 5/81 NM_007009.3 P4Q9BS86-1
ZPBPENST00000419417.5 linkuse as main transcriptc.495G>A p.Glu165= synonymous_variant 5/81 A2Q9BS86-2
ZPBPENST00000491129.5 linkuse as main transcriptn.240+24885G>A intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000684
AC:
104
AN:
151976
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00222
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000328
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00143
GnomAD3 exomes
AF:
0.000211
AC:
52
AN:
246146
Hom.:
0
AF XY:
0.000195
AC XY:
26
AN XY:
133612
show subpopulations
Gnomad AFR exome
AF:
0.00253
Gnomad AMR exome
AF:
0.0000586
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:
0.0000811
Gnomad OTH exome
AF:
0.000334
GnomAD4 exome
AF:
0.000112
AC:
163
AN:
1457480
Hom.:
0
Cov.:
31
AF XY:
0.000110
AC XY:
80
AN XY:
724796
show subpopulations
Gnomad4 AFR exome
AF:
0.00297
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000253
Gnomad4 SAS exome
AF:
0.0000702
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000216
Gnomad4 OTH exome
AF:
0.000316
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000684
AC:
104
AN:
152094
Hom.:
0
Cov.:
33
AF XY:
0.000659
AC XY:
49
AN XY:
74344
show subpopulations
Gnomad4 AFR
AF:
0.00222
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00142
Alfa
AF:
0.000158
Hom.:
0
Bravo
AF:
0.000616
Asia WGS
AF:
0.000578
AC:
2
AN:
3476
EpiCase
AF:
0.00
EpiControl
AF:
0.000179

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 12, 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
-0.50
Cadd
Benign
5.9
Dann
Benign
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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: rs201491108; hg19: chr7-50070896; API