chr7-50018292-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007009.3(ZPBP):​c.731G>T​(p.Gly244Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000041 in 1,609,624 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000043 ( 0 hom. )

Consequence

ZPBP
NM_007009.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.863
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ZPBPNM_007009.3 linkc.731G>T p.Gly244Val missense_variant 6/8 ENST00000046087.7 NP_008940.2 Q9BS86-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ZPBPENST00000046087.7 linkc.731G>T p.Gly244Val missense_variant 6/81 NM_007009.3 ENSP00000046087.2 Q9BS86-1
ZPBPENST00000419417.5 linkc.728G>T p.Gly243Val missense_variant 6/81 ENSP00000402071.1 Q9BS86-2
ZPBPENST00000491129.5 linkn.241-34773G>T intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.0000198
AC:
3
AN:
151618
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000442
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000440
AC:
11
AN:
250254
Hom.:
0
AF XY:
0.0000444
AC XY:
6
AN XY:
135276
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
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:
0.0000884
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000432
AC:
63
AN:
1458006
Hom.:
0
Cov.:
30
AF XY:
0.0000372
AC XY:
27
AN XY:
725418
show subpopulations
Gnomad4 AFR exome
AF:
0.0000300
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000198
AC:
3
AN:
151618
Hom.:
0
Cov.:
32
AF XY:
0.0000270
AC XY:
2
AN XY:
74010
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000442
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000848
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsOct 01, 2024The c.731G>T (p.G244V) alteration is located in exon 6 (coding exon 6) of the ZPBP gene. This alteration results from a G to T substitution at nucleotide position 731, causing the glycine (G) at amino acid position 244 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.087
BayesDel_addAF
Benign
-0.22
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.19
T;.
Eigen
Uncertain
0.30
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Benign
0.65
D
LIST_S2
Benign
0.72
T;T
M_CAP
Benign
0.013
T
MetaRNN
Benign
0.30
T;T
MetaSVM
Benign
-0.88
T
MutationAssessor
Uncertain
2.1
M;.
PrimateAI
Benign
0.44
T
PROVEAN
Benign
-1.7
N;N
REVEL
Benign
0.22
Sift
Benign
0.10
T;T
Sift4G
Benign
0.061
T;T
Polyphen
0.97
D;.
Vest4
0.37
MutPred
0.51
Gain of methylation at K243 (P = 0.0446);.;
MVP
0.72
MPC
0.46
ClinPred
0.44
T
GERP RS
3.2
Varity_R
0.13
gMVP
0.47

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.31
Details are displayed if max score is > 0.2
DS_AL_spliceai
0.31
Position offset: 24

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: rs760353111; hg19: chr7-50057888; API