Genetic Variant WNT3:c.323-420A>C (chr17-46770468-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030753.5(WNT3):c.323-420A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,052 control chromosomes in the GnomAD database, including 1,887 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 0.13 ( 1887 hom., cov: 32)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.171

Publications

39 publications found

Variant links:

Genes affected

WNT3 (HGNC:12782): (Wnt family member 3) 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 98% amino acid identity to mouse Wnt3 protein, and 84% to human WNT3A protein, another WNT gene product. The mouse studies show the requirement of Wnt3 in primary axis formation in the mouse. Studies of the gene expression suggest that this gene may play a key role in some cases of human breast, rectal, lung, and gastric cancer through activation of the WNT-beta-catenin-TCF signaling pathway. This gene is clustered with WNT15, another family member, in the chromosome 17q21 region. [provided by RefSeq, Jul 2008]

WNT3 links:

LRRC37A2 (HGNC:32404): (leucine rich repeat containing 37 member A2) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

LRRC37A2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030753.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	NM_030753.5	MANE Select	c.323-420A>C		intron	N/A	NP_110380.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WNT3	ENST00000225512.6	TSL:1 MANE Select	c.323-420A>C	intron	N/A	ENSP00000225512.5
WNT3	ENST00000706495.1		c.128-420A>C	intron	N/A	ENSP00000516418.1
WNT3	ENST00000706483.1		c.-233-420A>C	intron	N/A	ENSP00000516407.1

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20539

AN:

151934

Hom.:

1889

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0372

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.239

Gnomad EAS

AF:

0.000966

Gnomad SAS

AF:

0.0596

Gnomad FIN

AF:

0.0721

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.205

Gnomad OTH

AF:

0.172

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.135

AC:

20525

AN:

152052

Hom.:

1887

Cov.:

AF XY:

0.126

AC XY:

9371

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0371

AC:

1539

AN:

41470

American (AMR)

AF:

0.167

AC:

2553

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

829

AN:

3470

East Asian (EAS)

AF:

0.000968

AC:

AN:

5166

South Asian (SAS)

AF:

0.0593

AC:

284

AN:

4792

European-Finnish (FIN)

AF:

0.0721

AC:

763

AN:

10586

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.205

AC:

13899

AN:

67960

Other (OTH)

AF:

0.169

AC:

358

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

897

1793

2690

3586

4483

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.0387

Hom.:

Bravo

AF:

0.140

Asia WGS

AF:

0.0260

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

8.1

(source)

DANN

Benign

0.61

PhyloP100

0.17

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over