Variant chr12-14787450-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4

The NM_016312.3(WBP11):c.1541C>A(p.Pro514His) variant causes a missense change. The variant allele was found at a frequency of 0.00000145 in 1,380,558 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P514T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WBP11
NM_016312.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.17

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:

C12orf60 (HGNC:):

C12orf60 links:

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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;

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=0.30664867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WBP11	NM_016312.3 linkuse as main transcript	c.1541C>A	p.Pro514His	missense_variant	12/12	ENST00000261167.7
C12orf60	XM_047428389.1 linkuse as main transcript	c.-517+1243G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP11	ENST00000261167.7 linkuse as main transcript	c.1541C>A	p.Pro514His	missense_variant	12/12	1	NM_016312.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000145

AC:

AN:

1380558

Hom.:

Cov.:

AF XY:

0.00000148

AC XY:

AN XY:

677402

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000514

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 submitter

clinical testing

Ambry Genetics

Feb 21, 2024

The c.1541C>A (p.P514H) alteration is located in exon 12 (coding exon 11) of the WBP11 gene. This alteration results from a C to A substitution at nucleotide position 1541, causing the proline (P) at amino acid position 514 to be replaced by a histidine (H). 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

Pathogenic

0.63

BayesDel_addAF

Uncertain

0.031

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.068

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.74

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.31

MetaSVM

Uncertain

0.48

MutationAssessor

Uncertain

2.1

MutationTaster

Benign

0.97

D;D

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-2.2

REVEL

Uncertain

0.47

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.051

Polyphen

0.99

Vest4

0.39

MutPred

0.21

Loss of relative solvent accessibility (P = 0.0186);

MVP

0.12

MPC

0.67

ClinPred

0.88

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.21

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over