12-48966206-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003394.4(WNT10B):c.1059C>T(p.His353His) variant causes a synonymous change. The variant allele was found at a frequency of 0.37 in 1,613,570 control chromosomes in the GnomAD database, including 115,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 9136 hom., cov: 33)

Exomes 𝑓: 0.37 ( 106074 hom. )

Consequence

WNT10B
NM_003394.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 5.64

Publications

32 publications found

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 Gene-Disease associations (from GenCC):

split hand-foot malformation 6
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
tooth agenesis, selective, 8
Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
split hand-foot malformation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
tooth agenesis
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

WNT10B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 12-48966206-G-A is Benign according to our data. Variant chr12-48966206-G-A is described in ClinVar as Benign. ClinVar VariationId is 1175136.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT10B	NM_003394.4 link	c.1059C>T	p.His353His	synonymous_variant	Exon 5 of 5	ENST00000301061.9	NP_003385.2	O00744-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT10B	ENST00000301061.9 link	c.1059C>T	p.His353His	synonymous_variant	Exon 5 of 5	1	NM_003394.4	ENSP00000301061.4	O00744-1
WNT10B	ENST00000407467.5 link	c.*341C>T		3_prime_UTR_variant	Exon 6 of 6	2		ENSP00000384691.1	O00744-2
WNT10B	ENST00000403957.5 link	c.*341C>T		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000385980.1	B5MCC8

Frequencies

GnomAD3 genomes

AF:

0.326

AC:

49537

AN:

152070

Hom.:

9126

Cov.:

show subpopulations

Gnomad AFR

AF:

0.156

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.475

Gnomad ASJ

AF:

0.436

Gnomad EAS

AF:

0.466

Gnomad SAS

AF:

0.220

Gnomad FIN

AF:

0.376

Gnomad MID

AF:

0.396

Gnomad NFE

AF:

0.376

Gnomad OTH

AF:

0.357

GnomAD2 exomes

AF:

0.382

AC:

95727

AN:

250614

AF XY:

0.373

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.552

Gnomad ASJ exome

AF:

0.439

Gnomad EAS exome

AF:

0.465

Gnomad FIN exome

AF:

0.385

Gnomad NFE exome

AF:

0.388

Gnomad OTH exome

AF:

0.389

GnomAD4 exome

AF:

0.375

AC:

547613

AN:

1461380

Hom.:

106074

Cov.:

AF XY:

0.371

AC XY:

269867

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.150

AC:

5012

AN:

33478

American (AMR)

AF:

0.538

AC:

24049

AN:

44698

Ashkenazi Jewish (ASJ)

AF:

0.434

AC:

11348

AN:

26136

East Asian (EAS)

AF:

0.475

AC:

18841

AN:

39696

South Asian (SAS)

AF:

0.224

AC:

19283

AN:

86248

European-Finnish (FIN)

AF:

0.389

AC:

20657

AN:

53142

Middle Eastern (MID)

AF:

0.380

AC:

2191

AN:

5768

European-Non Finnish (NFE)

AF:

0.381

AC:

424156

AN:

1111830

Other (OTH)

AF:

0.366

AC:

22076

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

23251

46502

69752

93003

116254

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13216

26432

39648

52864

66080

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.326

AC:

49558

AN:

152190

Hom.:

9136

Cov.:

AF XY:

0.329

AC XY:

24500

AN XY:

74412

show subpopulations

African (AFR)

AF:

0.156

AC:

6469

AN:

41536

American (AMR)

AF:

0.476

AC:

7272

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

1513

AN:

3472

East Asian (EAS)

AF:

0.466

AC:

2411

AN:

5174

South Asian (SAS)

AF:

0.219

AC:

1060

AN:

4832

European-Finnish (FIN)

AF:

0.376

AC:

3979

AN:

10596

Middle Eastern (MID)

AF:

0.395

AC:

116

AN:

294

European-Non Finnish (NFE)

AF:

0.376

AC:

25586

AN:

67974

Other (OTH)

AF:

0.360

AC:

761

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

1653

3306

4960

6613

8266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

480

960

1440

1920

2400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.374

Hom.:

19685

Bravo

AF:

0.336

Asia WGS

AF:

0.363

AC:

1261

AN:

3478

EpiCase

AF:

0.389

EpiControl

AF:

0.393

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 02, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 19702932, 23104151, 29620206) -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

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

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Split hand-foot malformation 6

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Tooth agenesis, selective, 8

Benign:1

Dec 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

6.6

(source)

DANN

Benign

0.62

PhyloP100

5.6

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over