22-42027111-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_152613.3(WBP2NL):​c.860C>T​(p.Ser287Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WBP2NL
NM_152613.3 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.158
Variant links:
Genes affected
WBP2NL (HGNC:28389): (WBP2 N-terminal like) WBP2NL is a sperm-specific WW domain-binding protein that promotes meiotic resumption and pronuclear development during oocyte fertilization (Wu et al., 2007 [PubMed 17289678]).[supplied by OMIM, Mar 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1262736).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WBP2NLNM_152613.3 linkuse as main transcriptc.860C>T p.Ser287Phe missense_variant 6/6 ENST00000328823.13 NP_689826.2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WBP2NLENST00000328823.13 linkuse as main transcriptc.860C>T p.Ser287Phe missense_variant 6/61 NM_152613.3 ENSP00000332983 P1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461890
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 GeneticsFeb 23, 2023The c.860C>T (p.S287F) alteration is located in exon 6 (coding exon 6) of the WBP2NL gene. This alteration results from a C to T substitution at nucleotide position 860, causing the serine (S) at amino acid position 287 to be replaced by a phenylalanine (F). 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
0.11
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.54
CADD
Benign
11
DANN
Uncertain
1.0
DEOGEN2
Benign
0.0097
T;.
Eigen
Benign
-0.63
Eigen_PC
Benign
-0.77
FATHMM_MKL
Benign
0.032
N
LIST_S2
Benign
0.50
T;T
M_CAP
Benign
0.0096
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.0
M;.
MutationTaster
Benign
1.0
N;N
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-2.1
N;N
REVEL
Benign
0.044
Sift
Uncertain
0.0030
D;D
Sift4G
Benign
0.29
T;T
Polyphen
0.89
P;.
Vest4
0.083
MutPred
0.18
Loss of phosphorylation at S287 (P = 0.0171);.;
MVP
0.27
MPC
0.42
ClinPred
0.70
D
GERP RS
1.7
Varity_R
0.065
gMVP
0.31

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-42423115; API