Genetic Variant WNT3:c.323-1024C>A (chr17-46771072-G-T) – 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.323-1024C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,138 control chromosomes in the GnomAD database, including 32,545 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 0.63 ( 32545 hom., cov: 34)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.476

Publications

30 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=-0.79).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.798 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.323-1024C>A		intron	N/A	NP_110380.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
WNT3	ENST00000225512.6	TSL:1 MANE Select	c.323-1024C>A	intron	N/A	ENSP00000225512.5
WNT3	ENST00000706495.1		c.128-1024C>A	intron	N/A	ENSP00000516418.1
WNT3	ENST00000706483.1		c.-233-1024C>A	intron	N/A	ENSP00000516407.1

Frequencies

GnomAD3 genomes

AF:

0.628

AC:

95502

AN:

152020

Hom.:

32544

Cov.:

show subpopulations

Gnomad AFR

AF:

0.374

Gnomad AMI

AF:

0.666

Gnomad AMR

AF:

0.565

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.399

Gnomad SAS

AF:

0.819

Gnomad FIN

AF:

0.856

Gnomad MID

AF:

0.639

Gnomad NFE

AF:

0.762

Gnomad OTH

AF:

0.636

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

GnomAD4 genome

AF:

0.628

AC:

95530

AN:

152138

Hom.:

32545

Cov.:

AF XY:

0.634

AC XY:

47165

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.373

AC:

15487

AN:

41508

American (AMR)

AF:

0.565

AC:

8635

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.679

AC:

2355

AN:

3468

East Asian (EAS)

AF:

0.399

AC:

2049

AN:

5132

South Asian (SAS)

AF:

0.820

AC:

3960

AN:

4832

European-Finnish (FIN)

AF:

0.856

AC:

9078

AN:

10604

Middle Eastern (MID)

AF:

0.643

AC:

189

AN:

294

European-Non Finnish (NFE)

AF:

0.762

AC:

51821

AN:

67978

Other (OTH)

AF:

0.638

AC:

1349

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1654

3308

4962

6616

8270

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

768

1536

2304

3072

3840

<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:

0.730

Hom.:

28537

Bravo

AF:

0.584

Asia WGS

AF:

0.605

AC:

2106

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

7.5

(source)

DANN

Benign

0.69

PhyloP100

0.48

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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