Variant chr11-76194803-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_004626.3(WNT11):c.361G>A(p.Ala121Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00153 in 1,547,502 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0080 ( 18 hom., cov: 33)

Exomes 𝑓: 0.00083 ( 16 hom. )

Consequence

WNT11
NM_004626.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.71

Variant links:

Genes affected

WNT11 (HGNC:12776): (Wnt family member 11) 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 97%, 85%, and 63% amino acid identity with mouse, chicken, and Xenopus Wnt11 protein, respectively. This gene may play roles in the development of skeleton, kidney and lung, and is considered to be a plausible candidate gene for High Bone Mass Syndrome. [provided by RefSeq, Jul 2008]

WNT11 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.011740804).

BP6

Variant 11-76194803-C-T is Benign according to our data. Variant chr11-76194803-C-T is described in ClinVar as [Benign]. Clinvar id is 783636.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00797 (1213/152152) while in subpopulation AFR AF= 0.0281 (1165/41506). AF 95% confidence interval is 0.0267. There are 18 homozygotes in gnomad4. There are 584 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 1213 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT11	NM_004626.3 linkuse as main transcript	c.361G>A	p.Ala121Thr	missense_variant	3/5	ENST00000322563.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT11	ENST00000322563.8 linkuse as main transcript	c.361G>A	p.Ala121Thr	missense_variant	3/5	1	NM_004626.3	P1
	ENST00000527314.1 linkuse as main transcript	n.345C>T		non_coding_transcript_exon_variant	2/2	4

Frequencies

GnomAD3 genomes

AF:

0.00797

AC:

1212

AN:

152034

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0281

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000582

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00382

GnomAD3 exomes

AF:

0.00198

AC:

315

AN:

158828

Hom.:

AF XY:

0.00158

AC XY:

137

AN XY:

86866

show subpopulations

Gnomad AFR exome

AF:

0.0297

Gnomad AMR exome

AF:

0.00123

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000317

Gnomad SAS exome

AF:

0.0000885

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000438

Gnomad OTH exome

AF:

0.00254

GnomAD4 exome

AF:

0.000830

AC:

1158

AN:

1395350

Hom.:

Cov.:

AF XY:

0.000725

AC XY:

500

AN XY:

689352

show subpopulations

Gnomad4 AFR exome

AF:

0.0291

Gnomad4 AMR exome

AF:

0.00140

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000163

Gnomad4 SAS exome

AF:

0.0000758

Gnomad4 FIN exome

AF:

0.0000248

Gnomad4 NFE exome

AF:

0.0000516

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00797

AC:

1213

AN:

152152

Hom.:

Cov.:

AF XY:

0.00785

AC XY:

584

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0281

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000584

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00378

Alfa

AF:

0.00363

Hom.:

Bravo

AF:

0.00909

ESP6500AA

AF:

0.0215

AC:

ESP6500EA

AF:

0.000359

AC:

ExAC

AF:

0.00200

AC:

228

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.81

D;D

Eigen

Benign

-0.20

Eigen_PC

Benign

-0.19

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.012

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.8

L;.

MutationTaster

Benign

0.97

D;D

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.0

N;.

REVEL

Benign

0.29

Sift

Benign

0.21

T;.

Sift4G

Benign

0.12

T;T

Polyphen

0.76

P;.

Vest4

0.39

MVP

0.86

MPC

0.31

ClinPred

0.012

GERP RS

2.0

Varity_R

0.092

gMVP

0.79

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