chr12-48966364-G-A

Position:

chr12-48966364-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_003394.4(WNT10B):c.901C>T(p.Pro301Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0193 in 1,614,224 control chromosomes in the GnomAD database, including 402 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.012 ( 31 hom., cov: 32)

Exomes 𝑓: 0.020 ( 371 hom. )

Consequence

WNT10B
NM_003394.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 6.38

Variant links:

Genes affected

WNT10B (HGNC:12775): (Wnt family member 10B) 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 may be involved in breast cancer, and its protein signaling is likely a molecular switch that governs adipogenesis. This protein is 96% identical to the mouse Wnt10b protein at the amino acid level. This gene is clustered with another family member, WNT1, in the chromosome 12q13 region. [provided by RefSeq, Jul 2008]

WNT10B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006138742).

BP6

Variant 12-48966364-G-A is Benign according to our data. Variant chr12-48966364-G-A is described in ClinVar as [Benign]. Clinvar id is 782957.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-48966364-G-A is described in Lovd as [Benign]. Variant chr12-48966364-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0121 (1850/152344) while in subpopulation NFE AF= 0.0194 (1322/68038). AF 95% confidence interval is 0.0186. There are 31 homozygotes in gnomad4. There are 869 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 31 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT10B	NM_003394.4 link	c.901C>T	p.Pro301Ser	missense_variant	5/5	ENST00000301061.9	NP_003385.2	O00744-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WNT10B	ENST00000301061.9 link	c.901C>T	p.Pro301Ser	missense_variant	5/5	1	NM_003394.4	ENSP00000301061.4	O00744-1
WNT10B	ENST00000407467 link	c.*183C>T		3_prime_UTR_variant	6/6	2		ENSP00000384691.1	O00744-2
WNT10B	ENST00000403957 link	c.*183C>T		3_prime_UTR_variant	6/6	5		ENSP00000385980.1	B5MCC8

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1850

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00844

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0194

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0194

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0106

AC:

2655

AN:

250728

Hom.:

AF XY:

0.0105

AC XY:

1423

AN XY:

135708

show subpopulations

Gnomad AFR exome

AF:

0.00305

Gnomad AMR exome

AF:

0.00622

Gnomad ASJ exome

AF:

0.00398

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0190

Gnomad NFE exome

AF:

0.0164

Gnomad OTH exome

AF:

0.0139

GnomAD4 exome

AF:

0.0201

AC:

29319

AN:

1461880

Hom.:

371

Cov.:

AF XY:

0.0192

AC XY:

13950

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.00296

Gnomad4 AMR exome

AF:

0.00657

Gnomad4 ASJ exome

AF:

0.00432

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.0173

Gnomad4 NFE exome

AF:

0.0240

Gnomad4 OTH exome

AF:

0.0199

GnomAD4 genome

AF:

0.0121

AC:

1850

AN:

152344

Hom.:

Cov.:

AF XY:

0.0117

AC XY:

869

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.00385

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0194

Gnomad4 NFE

AF:

0.0194

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.0157

Hom.:

Bravo

AF:

0.0111

TwinsUK

AF:

0.0221

AC:

ALSPAC

AF:

0.0265

AC:

102

ESP6500AA

AF:

0.00318

AC:

ESP6500EA

AF:

0.0155

AC:

133

ExAC

AF:

0.00968

AC:

1175

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.0172

EpiControl

AF:

0.0165

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 11, 2020	This variant is associated with the following publications: (PMID: 20579865, 16477437, 23104151) -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

- -

WNT10B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 26, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.89

DEOGEN2

Benign

0.23

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.056

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.68

MetaRNN

Benign

0.0061

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.73

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.10

REVEL

Benign

0.24

Sift

Benign

0.66

Sift4G

Benign

0.33

Polyphen

0.027

Vest4

0.16

MPC

0.73

ClinPred

0.017

GERP RS

4.4

Varity_R

0.075

gMVP

0.42

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