Variant 10-102810037-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001083913.2(WBP1L):c.338C>T(p.Ala113Val) variant causes a missense change. The variant allele was found at a frequency of 0.00008 in 1,612,322 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 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000073 ( 0 hom. )

Consequence

WBP1L
NM_001083913.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.96

Variant links:

Genes affected

WBP1L (HGNC:23510): (WW domain binding protein 1 like) Predicted to enable ubiquitin protein ligase binding activity. Predicted to act upstream of or within CXCL12-activated CXCR4 signaling pathway; hemopoiesis; and positive regulation of protein ubiquitination. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

WBP1L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08607876).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WBP1L	NM_001083913.2 linkuse as main transcript	c.338C>T	p.Ala113Val	missense_variant	3/4	ENST00000448841.7
WBP1L	NM_017787.5 linkuse as main transcript	c.275C>T	p.Ala92Val	missense_variant	3/4
WBP1L	XM_011539913.3 linkuse as main transcript	c.311C>T	p.Ala104Val	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP1L	ENST00000448841.7 linkuse as main transcript	c.338C>T	p.Ala113Val	missense_variant	3/4	2	NM_001083913.2	A2	Q9NX94-2
WBP1L	ENST00000369889.5 linkuse as main transcript	c.275C>T	p.Ala92Val	missense_variant	3/4	1		P4	Q9NX94-1
WBP1L	ENST00000647664.1 linkuse as main transcript	c.338C>T	p.Ala113Val	missense_variant, NMD_transcript_variant	3/8

Frequencies

GnomAD3 genomes

AF:

0.000151

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00137

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:

0.000156

AC:

AN:

249436

Hom.:

AF XY:

0.000104

AC XY:

AN XY:

134848

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00102

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:

0.0000266

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000726

AC:

106

AN:

1460126

Hom.:

Cov.:

AF XY:

0.0000578

AC XY:

AN XY:

726422

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00126

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:

0.0000396

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.000151

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00137

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

Bravo

AF:

0.000200

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 26, 2022

The c.338C>T (p.A113V) alteration is located in exon 3 (coding exon 3) of the WBP1L gene. This alteration results from a C to T substitution at nucleotide position 338, causing the alanine (A) at amino acid position 113 to be replaced by a valine (V). 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

0.16

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.38

Cadd

Uncertain

Dann

Uncertain

1.0

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.31

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D

M_CAP

Benign

0.0067

MetaRNN

Benign

0.086

T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.9

N;N

REVEL

Benign

0.068

Sift

Benign

0.11

T;T

Sift4G

Benign

0.15

T;T

Polyphen

0.12

B;B

Vest4

0.65

MutPred

0.27

.;Gain of sheet (P = 0.1539);

MVP

0.043

MPC

0.29

ClinPred

0.083

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.11

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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