12-48966411-A-G

Position:

chr12-48966411-A-G

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4BP6BS1

The NM_003394.4(WNT10B):c.854T>C(p.Ile285Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000615 in 1,614,030 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 Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.00053 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00062 ( 1 hom. )

Consequence

WNT10B
NM_003394.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.12

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30538112).

BP6

Variant 12-48966411-A-G is Benign according to our data. Variant chr12-48966411-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 2069153.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.000532 (81/152310) while in subpopulation SAS AF= 0.00186 (9/4830). AF 95% confidence interval is 0.000971. There are 1 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT10B	NM_003394.4 linkuse as main transcript	c.854T>C	p.Ile285Thr	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 linkuse as main transcript	c.854T>C	p.Ile285Thr	missense_variant	5/5	1	NM_003394.4	ENSP00000301061.4	O00744-1
WNT10B	ENST00000407467.5 linkuse as main transcript	c.*136T>C		3_prime_UTR_variant	6/6	2		ENSP00000384691.1	O00744-2
WNT10B	ENST00000403957.5 linkuse as main transcript	c.*136T>C		3_prime_UTR_variant	6/6	5		ENSP00000385980.1	B5MCC8

Frequencies

GnomAD3 genomes

AF:

0.000526

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00165

Gnomad FIN

AF:

0.0000942

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000794

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.000631

AC:

158

AN:

250436

Hom.:

AF XY:

0.000796

AC XY:

108

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.0000623

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.0000995

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00114

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000894

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.000623

AC:

911

AN:

1461720

Hom.:

Cov.:

AF XY:

0.000692

AC XY:

503

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000335

Gnomad4 ASJ exome

AF:

0.000344

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.000962

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.000665

Gnomad4 OTH exome

AF:

0.000596

GnomAD4 genome

AF:

0.000532

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000564

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000144

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00186

Gnomad4 FIN

AF:

0.0000942

Gnomad4 NFE

AF:

0.000794

Gnomad4 OTH

AF:

0.00236

Alfa

AF:

0.000637

Hom.:

Bravo

AF:

0.000506

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000749

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00104

EpiControl

AF:

0.00160

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not provided

Uncertain:1Benign:1

Uncertain significance, criteria provided, single submitter	clinical testing	GeneDx	Jul 13, 2022	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 14, 2024	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.65

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.80

Eigen

Uncertain

0.53

Eigen_PC

Uncertain

0.52

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.75

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.31

MetaSVM

Uncertain

-0.10

MutationAssessor

Uncertain

2.6

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-3.4

REVEL

Uncertain

0.56

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.0030

Polyphen

0.87

Vest4

0.67

MVP

0.94

MPC

1.1

ClinPred

0.087

GERP RS

4.4

Varity_R

0.58

gMVP

0.60

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