Variant 13-41076202-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_007187.5(WBP4):c.721T>G(p.Ser241Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000373 in 1,608,606 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

WBP4
NM_007187.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.335

Variant links:

Genes affected

WBP4 (HGNC:12739): (WW domain binding protein 4) This gene encodes WW domain-containing binding protein 4. The WW domain represents a small and compact globular structure that interacts with proline-rich ligands. This encoded protein is a general spliceosomal protein that may play a role in cross-intron bridging of U1 and U2 snRNPs in the spliceosomal complex A. [provided by RefSeq, Jul 2008]

WBP4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020482928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WBP4	NM_007187.5 linkuse as main transcript	c.721T>G	p.Ser241Ala	missense_variant	8/10	ENST00000379487.5
WBP4	XM_005266245.3 linkuse as main transcript	c.814T>G	p.Ser272Ala	missense_variant	8/10
WBP4	XM_047430071.1 linkuse as main transcript	c.253T>G	p.Ser85Ala	missense_variant	3/5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WBP4	ENST00000379487.5 linkuse as main transcript	c.721T>G	p.Ser241Ala	missense_variant	8/10	1	NM_007187.5	P1	O75554-1

Frequencies

GnomAD3 genomes

AF:

0.000219

AC:

AN:

150820

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000658

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000266

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:

0.0000147

Gnomad OTH

AF:

0.000488

GnomAD3 exomes

AF:

0.0000604

AC:

AN:

248502

Hom.:

AF XY:

0.0000670

AC XY:

AN XY:

134348

show subpopulations

Gnomad AFR exome

AF:

0.000742

Gnomad AMR exome

AF:

0.0000594

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:

0.00

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1457696

Hom.:

Cov.:

AF XY:

0.0000152

AC XY:

AN XY:

725140

show subpopulations

Gnomad4 AFR exome

AF:

0.000482

Gnomad4 AMR exome

AF:

0.000160

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:

0.00

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.000225

AC:

AN:

150910

Hom.:

Cov.:

AF XY:

0.000163

AC XY:

AN XY:

73630

show subpopulations

Gnomad4 AFR

AF:

0.000680

Gnomad4 AMR

AF:

0.000265

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000484

Alfa

AF:

0.000132

Hom.:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

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

Oct 26, 2022

The c.721T>G (p.S241A) alteration is located in exon 8 (coding exon 8) of the WBP4 gene. This alteration results from a T to G substitution at nucleotide position 721, causing the serine (S) at amino acid position 241 to be replaced by an alanine (A). 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

0.061

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.64

CADD

Benign

2.0

DANN

Benign

0.94

DEOGEN2

Benign

0.012

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.088

LIST_S2

Benign

0.22

M_CAP

Benign

0.0048

MetaRNN

Benign

0.020

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

REVEL

Benign

0.064

Sift

Benign

0.10

Polyphen

0.0010

Vest4

0.11

MVP

0.22

MPC

0.024

ClinPred

0.011

GERP RS

-3.1

Varity_R

0.044

gMVP

0.14

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