dbSNP rs3793771: WNT8B:p.Cys11Ser (chr10-100463200-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003393.4(WNT8B):c.32G>C(p.Cys11Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.221 in 1,612,156 control chromosomes in the GnomAD database, including 40,337 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.21 ( 3554 hom., cov: 32)

Exomes 𝑓: 0.22 ( 36783 hom. )

Consequence

WNT8B
NM_003393.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.66

Variant links:

Genes affected

WNT8B (HGNC:12789): (Wnt family member 8B) The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. This gene is a member of the WNT gene family. It encodes a protein which shows 95%, 86% and 71% amino acid identity to the mouse, zebrafish and Xenopus Wnt8B proteins, respectively. The expression patterns of the human and mouse genes appear identical and are restricted to the developing brain. The chromosomal location of this gene to 10q24 suggests it as a candidate gene for partial epilepsy. [provided by RefSeq, Jul 2008]

WNT8B links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00332734).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT8B	NM_003393.4 link	c.32G>C	p.Cys11Ser	missense_variant	Exon 1 of 6	ENST00000343737.6	NP_003384.2	Q93098A0A384NKY7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT8B	ENST00000343737.6 link	c.32G>C	p.Cys11Ser	missense_variant	Exon 1 of 6	1	NM_003393.4	ENSP00000340677.5		Q93098

Frequencies

GnomAD3 genomes

AF:

0.213

AC:

32384

AN:

151952

Hom.:

3535

Cov.:

show subpopulations

Gnomad AFR

AF:

0.209

Gnomad AMI

AF:

0.226

Gnomad AMR

AF:

0.182

Gnomad ASJ

AF:

0.204

Gnomad EAS

AF:

0.130

Gnomad SAS

AF:

0.231

Gnomad FIN

AF:

0.223

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.206

GnomAD3 exomes

AF:

0.208

AC:

52131

AN:

250590

Hom.:

5744

AF XY:

0.211

AC XY:

28516

AN XY:

135442

show subpopulations

Gnomad AFR exome

AF:

0.205

Gnomad AMR exome

AF:

0.157

Gnomad ASJ exome

AF:

0.201

Gnomad EAS exome

AF:

0.127

Gnomad SAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.236

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.212

GnomAD4 exome

AF:

0.222

AC:

323800

AN:

1460084

Hom.:

36783

Cov.:

AF XY:

0.223

AC XY:

161912

AN XY:

726382

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.160

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.156

Gnomad4 SAS exome

AF:

0.231

Gnomad4 FIN exome

AF:

0.234

Gnomad4 NFE exome

AF:

0.226

Gnomad4 OTH exome

AF:

0.219

GnomAD4 genome

AF:

0.213

AC:

32427

AN:

152072

Hom.:

3554

Cov.:

AF XY:

0.213

AC XY:

15829

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.210

Gnomad4 AMR

AF:

0.182

Gnomad4 ASJ

AF:

0.204

Gnomad4 EAS

AF:

0.130

Gnomad4 SAS

AF:

0.231

Gnomad4 FIN

AF:

0.223

Gnomad4 NFE

AF:

0.227

Gnomad4 OTH

AF:

0.204

Alfa

AF:

0.224

Hom.:

2924

Bravo

AF:

0.211

TwinsUK

AF:

0.224

AC:

830

ALSPAC

AF:

0.220

AC:

846

ESP6500AA

AF:

0.203

AC:

894

ESP6500EA

AF:

0.227

AC:

1950

ExAC

AF:

0.212

AC:

25801

Asia WGS

AF:

0.193

AC:

671

AN:

3478

EpiCase

AF:

0.214

EpiControl

AF:

0.214

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.16

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.14

MetaRNN

Benign

0.0033

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.69

PrimateAI

Benign

0.32

PROVEAN

Benign

0.15

REVEL

Benign

0.11

Sift

Benign

0.22

Sift4G

Benign

0.39

Polyphen

0.0

Vest4

0.021

MutPred

0.20

Loss of catalytic residue at L12 (P = 0.0085);

MPC

1.0

ClinPred

0.0046

GERP RS

4.7

Varity_R

0.073

gMVP

0.49

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over