Genetic Variant WNT11:p.Arg190Ser (chr11-76194596-G-T) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004626.3(WNT11):c.568C>A(p.Arg190Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000143 in 1,397,978 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R190C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

WNT11
NM_004626.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.75

Publications

0 publications found

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:

ENSG00000254933 (HGNC:):

ENSG00000254933 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004626.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT11	NM_004626.3	MANE Select	c.568C>A	p.Arg190Ser	missense	Exon 3 of 5	NP_004617.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WNT11	ENST00000322563.8	TSL:1 MANE Select	c.568C>A	p.Arg190Ser	missense	Exon 3 of 5	ENSP00000325526.3	O96014
WNT11	ENST00000961018.1		c.598C>A	p.Arg200Ser	missense	Exon 4 of 6	ENSP00000631077.1
WNT11	ENST00000961028.1		c.598C>A	p.Arg200Ser	missense	Exon 4 of 6	ENSP00000631087.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000143

AC:

AN:

1397978

Hom.:

Cov.:

AF XY:

0.00000145

AC XY:

AN XY:

689482

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31544

American (AMR)

AF:

0.00

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25176

East Asian (EAS)

AF:

0.00

AC:

AN:

35736

South Asian (SAS)

AF:

0.00

AC:

AN:

79170

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49276

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4586

European-Non Finnish (NFE)

AF:

0.00000185

AC:

AN:

1078918

Other (OTH)

AF:

0.00

AC:

AN:

57870

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.38

BayesDel_addAF

Uncertain

0.024

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

Eigen

Benign

0.060

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.59

MetaSVM

Benign

-0.64

MutationAssessor

Benign

0.90

PhyloP100

6.7

PrimateAI

Benign

0.40

PROVEAN

Benign

0.31

REVEL

Uncertain

0.38

Sift

Uncertain

0.020

Sift4G

Uncertain

0.026

Polyphen

0.059

Vest4

0.63

MutPred

0.63

Loss of MoRF binding (P = 0.0186)

MVP

0.91

MPC

0.40

ClinPred

0.93

GERP RS

5.2

Varity_R

0.28

gMVP

0.70

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over