chr12-14789091-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_016312.3(WBP11):​c.1352G>A​(p.Arg451Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000583 in 1,372,436 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000058 ( 0 hom. )

Consequence

WBP11
NM_016312.3 missense

Scores

1
9
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.29
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 -4 ACMG points.

BS2
High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WBP11NM_016312.3 linkc.1352G>A p.Arg451Gln missense_variant Exon 11 of 12 ENST00000261167.7 NP_057396.1 Q9Y2W2A0A024RAW9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WBP11ENST00000261167.7 linkc.1352G>A p.Arg451Gln missense_variant Exon 11 of 12 1 NM_016312.3 ENSP00000261167.2 Q9Y2W2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000588
AC:
1
AN:
170196
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
94140
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:
0.0000519
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000583
AC:
8
AN:
1372436
Hom.:
0
Cov.:
32
AF XY:
0.00000294
AC XY:
2
AN XY:
680474
show subpopulations
Gnomad4 AFR exome
AF:
0.0000370
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000143
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000555
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Dec 08, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1352G>A (p.R451Q) alteration is located in exon 11 (coding exon 10) of the WBP11 gene. This alteration results from a G to A substitution at nucleotide position 1352, causing the arginine (R) at amino acid position 451 to be replaced by a glutamine (Q). 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
Uncertain
0.47
BayesDel_addAF
Uncertain
0.043
T
BayesDel_noAF
Benign
-0.18
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.031
T
Eigen
Uncertain
0.51
Eigen_PC
Uncertain
0.54
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.76
T
M_CAP
Benign
0.017
T
MetaRNN
Uncertain
0.52
D
MetaSVM
Uncertain
0.14
D
MutationAssessor
Benign
1.8
L
PrimateAI
Uncertain
0.74
T
PROVEAN
Benign
-1.4
N
REVEL
Uncertain
0.41
Sift
Benign
0.37
T
Sift4G
Benign
0.21
T
Polyphen
1.0
D
Vest4
0.58
MutPred
0.28
Loss of methylation at R451 (P = 0.0092);
MVP
0.28
MPC
0.67
ClinPred
0.89
D
GERP RS
4.7
Varity_R
0.21
gMVP
0.34

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: rs199518864; hg19: chr12-14942025; API