Genetic Variant WNT11:p.Arg324Leu (chr11-76187159-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004626.3(WNT11):c.971G>T(p.Arg324Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,370 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. 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. R324H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

WNT11
NM_004626.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.13

Publications

2 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20112678).

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.971G>T	p.Arg324Leu	missense	Exon 5 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.971G>T	p.Arg324Leu	missense	Exon 5 of 5	ENSP00000325526.3	O96014
WNT11	ENST00000961018.1		c.1001G>T	p.Arg334Leu	missense	Exon 6 of 6	ENSP00000631077.1
WNT11	ENST00000961028.1		c.1001G>T	p.Arg334Leu	missense	Exon 6 of 6	ENSP00000631087.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000402

AC:

AN:

248818

AF XY:

0.00000742

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000514

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1459370

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726100

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50960

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1111980

Other (OTH)

AF:

0.00

AC:

AN:

60372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.046

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.60

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.24

FATHMM_MKL

Benign

0.68

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.037

MetaRNN

Benign

0.20

MetaSVM

Benign

-0.85

MutationAssessor

Benign

0.81

PhyloP100

2.1

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.9

REVEL

Benign

0.14

Sift

Benign

0.15

Sift4G

Benign

0.18

Polyphen

0.030

Vest4

0.14

MutPred

0.53

Loss of disorder (P = 0.041)

MVP

0.85

MPC

0.38

ClinPred

0.48

GERP RS

2.7

Varity_R

0.14

gMVP

0.35

Mutation Taster

=82/18

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over