Genetic Variant NM_004626.3:c.408C>T (chr11-76194756-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_004626.3(WNT11):c.408C>T(p.Pro136Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.26 in 1,553,706 control chromosomes in the GnomAD database, including 53,486 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.23 ( 4347 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49139 hom. )

Consequence

WNT11
NM_004626.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.746

Publications

26 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: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP7

Synonymous conserved (PhyloP=0.746 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.315 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT11	NM_004626.3 link	c.408C>T	p.Pro136Pro	synonymous_variant	Exon 3 of 5	ENST00000322563.8	NP_004617.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT11	ENST00000322563.8 link	c.408C>T	p.Pro136Pro	synonymous_variant	Exon 3 of 5	1	NM_004626.3	ENSP00000325526.3
ENSG00000254933	ENST00000527314.1 link	n.298G>A		non_coding_transcript_exon_variant	Exon 2 of 2	4

Frequencies

GnomAD3 genomes

AF:

0.229

AC:

34735

AN:

151940

Hom.:

4339

Cov.:

show subpopulations

Gnomad AFR

AF:

0.131

Gnomad AMI

AF:

0.331

Gnomad AMR

AF:

0.321

Gnomad ASJ

AF:

0.293

Gnomad EAS

AF:

0.228

Gnomad SAS

AF:

0.265

Gnomad FIN

AF:

0.294

Gnomad MID

AF:

0.290

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.251

GnomAD2 exomes

AF:

0.268

AC:

42756

AN:

159648

AF XY:

0.268

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.339

Gnomad ASJ exome

AF:

0.302

Gnomad EAS exome

AF:

0.204

Gnomad FIN exome

AF:

0.300

Gnomad NFE exome

AF:

0.257

Gnomad OTH exome

AF:

0.265

GnomAD4 exome

AF:

0.263

AC:

368931

AN:

1401648

Hom.:

49139

Cov.:

AF XY:

0.264

AC XY:

182471

AN XY:

691900

show subpopulations

African (AFR)

AF:

0.125

AC:

3990

AN:

31908

American (AMR)

AF:

0.335

AC:

12279

AN:

36668

Ashkenazi Jewish (ASJ)

AF:

0.299

AC:

7519

AN:

25180

East Asian (EAS)

AF:

0.275

AC:

9948

AN:

36230

South Asian (SAS)

AF:

0.272

AC:

21653

AN:

79476

European-Finnish (FIN)

AF:

0.295

AC:

14120

AN:

47856

Middle Eastern (MID)

AF:

0.282

AC:

1196

AN:

4240

European-Non Finnish (NFE)

AF:

0.262

AC:

283044

AN:

1082050

Other (OTH)

AF:

0.262

AC:

15182

AN:

58040

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

18305

36609

54914

73218

91523

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9772

19544

29316

39088

48860

<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:

0.229

AC:

34769

AN:

152058

Hom.:

4347

Cov.:

AF XY:

0.230

AC XY:

17129

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.131

AC:

5437

AN:

41494

American (AMR)

AF:

0.322

AC:

4927

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.293

AC:

1019

AN:

3472

East Asian (EAS)

AF:

0.228

AC:

1169

AN:

5132

South Asian (SAS)

AF:

0.265

AC:

1277

AN:

4826

European-Finnish (FIN)

AF:

0.294

AC:

3114

AN:

10586

Middle Eastern (MID)

AF:

0.295

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.249

AC:

16907

AN:

67948

Other (OTH)

AF:

0.252

AC:

532

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1354

2709

4063

5418

6772

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

374

748

1122

1496

1870

<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:

0.250

Hom.:

1616

Bravo

AF:

0.229

Asia WGS

AF:

0.266

AC:

922

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

0.75

Mutation Taster

=99/1

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

Computational scores

Splicing

Publications

Other links and lift over