Variant 10-102810016-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001083913.2(WBP1L):c.317G>A(p.Arg106Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000359 in 1,613,662 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00038 ( 2 hom. )

Consequence

WBP1L
NM_001083913.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.15

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17141742).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WBP1L	NM_001083913.2 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/4	ENST00000448841.7	NP_001077382.1
WBP1L	NM_017787.5 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	3/4		NP_060257.4
WBP1L	XM_011539913.3 linkuse as main transcript	c.290G>A	p.Arg97Gln	missense_variant	3/4		XP_011538215.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WBP1L	ENST00000448841.7 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant	3/4	2	NM_001083913.2	ENSP00000414721	A2	Q9NX94-2
WBP1L	ENST00000369889.5 linkuse as main transcript	c.254G>A	p.Arg85Gln	missense_variant	3/4	1		ENSP00000358905	P4	Q9NX94-1
WBP1L	ENST00000647664.1 linkuse as main transcript	c.317G>A	p.Arg106Gln	missense_variant, NMD_transcript_variant	3/8			ENSP00000498131

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000283

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000323

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000263

AC:

AN:

250982

Hom.:

AF XY:

0.000273

AC XY:

AN XY:

135680

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000490

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.000361

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000376

AC:

549

AN:

1461406

Hom.:

Cov.:

AF XY:

0.000384

AC XY:

279

AN XY:

727066

show subpopulations

Gnomad4 AFR exome

AF:

0.0000598

Gnomad4 AMR exome

AF:

0.0000448

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000533

Gnomad4 FIN exome

AF:

0.000188

Gnomad4 NFE exome

AF:

0.000409

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000197

AC:

AN:

152256

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0000722

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000283

Gnomad4 NFE

AF:

0.000323

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000323

Hom.:

Bravo

AF:

0.000174

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000349

AC:

ExAC

AF:

0.000288

AC:

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000830

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

Jun 18, 2021

The c.317G>A (p.R106Q) alteration is located in exon 3 (coding exon 3) of the WBP1L gene. This alteration results from a G to A substitution at nucleotide position 317, causing the arginine (R) at amino acid position 106 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

Benign

0.17

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.16

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0074

.;T

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

D;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.17

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.0

.;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.19

Sift

Benign

0.14

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.40

B;B

Vest4

0.74

MVP

0.043

MPC

0.37

ClinPred

0.029

GERP RS

5.8

Varity_R

0.11

gMVP

0.72

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