12-14787204-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PP2BP4_ModerateBS2

The NM_016312.3(WBP11):​c.1787C>T​(p.Pro596Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,613,988 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 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

WBP11
NM_016312.3 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18
Variant links:
Genes affected
WBP11 (HGNC:16461): (WW domain binding protein 11) This gene encodes a nuclear protein, which colocalizes with mRNA splicing factors and intermediate filament-containing perinuclear networks. This protein has 95% amino acid sequence identity to the mouse Wbp11 protein. It contains two proline-rich regions that bind to the WW domain of Npw38, a nuclear protein, and thus this protein is also called Npw38-binding protein NpwBP. The Npw38-NpwBP complex may function as a component of an mRNA factory in the nucleus. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PP2
Missense variant in gene, where missense usually causes diseases (based on misZ statistic), WBP11. . Gene score misZ 2.9803 (greater than the threshold 3.09). Trascript score misZ 3.4119 (greater than threshold 3.09). GenCC has associacion of gene with vertebral, cardiac, tracheoesophageal, renal, and limb defects.
BP4
Computational evidence support a benign effect (MetaRNN=0.13895786).
BS2
High AC in GnomAdExome4 at 21 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WBP11NM_016312.3 linkuse as main transcriptc.1787C>T p.Pro596Leu missense_variant 12/12 ENST00000261167.7 NP_057396.1 Q9Y2W2A0A024RAW9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WBP11ENST00000261167.7 linkuse as main transcriptc.1787C>T p.Pro596Leu missense_variant 12/121 NM_016312.3 ENSP00000261167.2 Q9Y2W2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152166
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:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000795
AC:
2
AN:
251482
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135916
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
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:
0.0000176
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000144
AC:
21
AN:
1461822
Hom.:
0
Cov.:
31
AF XY:
0.0000138
AC XY:
10
AN XY:
727212
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:
0.0000180
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152166
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74346
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:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 24, 2023The c.1787C>T (p.P596L) alteration is located in exon 12 (coding exon 11) of the WBP11 gene. This alteration results from a C to T substitution at nucleotide position 1787, causing the proline (P) at amino acid position 596 to be replaced by a leucine (L). 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
0.062
BayesDel_addAF
Pathogenic
0.23
D
BayesDel_noAF
Uncertain
0.11
CADD
Benign
21
DANN
Benign
0.96
DEOGEN2
Benign
0.024
T
Eigen
Benign
0.060
Eigen_PC
Benign
0.21
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.074
D
MetaRNN
Benign
0.14
T
MetaSVM
Uncertain
0.37
D
MutationAssessor
Benign
0.38
N
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-0.97
N
REVEL
Uncertain
0.48
Sift
Benign
0.79
T
Sift4G
Benign
0.42
T
Polyphen
0.16
B
Vest4
0.20
MutPred
0.17
Loss of relative solvent accessibility (P = 0.0306);
MVP
0.88
MPC
0.67
ClinPred
0.41
T
GERP RS
5.1
Varity_R
0.088
gMVP
0.052

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: rs769221605; hg19: chr12-14940138; API