Variant 12-14789091-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2

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

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]

WBP11 links:

C12orf60 (HGNC:):

C12orf60 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 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.

BS2

High AC in GnomAdExome4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WBP11	NM_016312.3 linkuse as main transcript	c.1352G>A	p.Arg451Gln	missense_variant	11/12	ENST00000261167.7
C12orf60	XM_047428389.1 linkuse as main transcript	c.-517+2884C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP11	ENST00000261167.7 linkuse as main transcript	c.1352G>A	p.Arg451Gln	missense_variant	11/12	1	NM_016312.3	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000588

AC:

AN:

170196

Hom.:

AF XY:

0.00

AC XY:

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:

AN:

1372436

Hom.:

Cov.:

AF XY:

0.00000294

AC XY:

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.:

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

Dec 08, 2023

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

BayesDel_noAF

Benign

-0.18

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.54

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.76

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.52

MetaSVM

Uncertain

0.14

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.4

REVEL

Uncertain

0.41

Sift

Benign

0.37

Sift4G

Benign

0.21

Polyphen

1.0

Vest4

0.58

MutPred

0.28

Loss of methylation at R451 (P = 0.0092);

MVP

0.28

MPC

0.67

ClinPred

0.89

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.

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