Genetic Variant WBP11:p.Pro459Leu (chr12-14789067-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_016312.3(WBP11):c.1376C>T(p.Pro459Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WBP11
NM_016312.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 9.22

Publications

0 publications found

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]

WBP11 links:

GUCY2C-AS1 (HGNC:56054): (GUCY2C antisense RNA 1)

GUCY2C-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016312.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WBP11	NM_016312.3	MANE Select	c.1376C>T	p.Pro459Leu	missense	Exon 11 of 12	NP_057396.1	Q9Y2W2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WBP11	ENST00000261167.7	TSL:1 MANE Select	c.1376C>T	p.Pro459Leu	missense	Exon 11 of 12	ENSP00000261167.2	Q9Y2W2
WBP11	ENST00000858075.1		c.1376C>T	p.Pro459Leu	missense	Exon 12 of 13	ENSP00000528134.1
WBP11	ENST00000918140.1		c.1376C>T	p.Pro459Leu	missense	Exon 11 of 12	ENSP00000588199.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

164698

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1365186

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

676470

African (AFR)

AF:

0.00

AC:

AN:

26738

American (AMR)

AF:

0.00

AC:

AN:

22100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22756

East Asian (EAS)

AF:

0.00

AC:

AN:

32258

South Asian (SAS)

AF:

0.00

AC:

AN:

68394

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52728

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5462

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078406

Other (OTH)

AF:

0.00

AC:

AN:

56344

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.91

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.35

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.72

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.84

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.59

MetaSVM

Uncertain

0.59

MutationAssessor

Uncertain

2.5

PhyloP100

9.2

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-3.7

REVEL

Uncertain

0.52

Sift

Pathogenic

0.0

Sift4G

Benign

0.084

Polyphen

1.0

Vest4

0.61

MutPred

0.28

Loss of glycosylation at P459 (P = 0.0213)

MVP

0.25

MPC

0.59

ClinPred

0.98

GERP RS

4.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.50

Mutation Taster

=64/36

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over