Genetic Variant NM_030753.5:c.81-16912C>T (chr17-46790821-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

-12

BP4_StrongBA1

The NM_030753.5(WNT3):c.81-16912C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 152,088 control chromosomes in the GnomAD database, including 20,502 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 0.51 ( 20502 hom., cov: 33)

Consequence

WNT3
NM_030753.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.688

Publications

21 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=-0.92).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT3	NM_030753.5 link	c.81-16912C>T		intron_variant	Intron 1 of 4	ENST00000225512.6	NP_110380.1	P56703
LRRC37A2	XM_024450773.2 link	c.4809+240302G>A		intron_variant	Intron 10 of 10		XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT3	ENST00000225512.6 link	c.81-16912C>T	intron_variant	Intron 1 of 4	1	NM_030753.5	ENSP00000225512.5	P56703
WNT3	ENST00000706495.1 link	c.-115-16912C>T	intron_variant	Intron 2 of 5			ENSP00000516418.1	A0A9L9PXJ3
WNT3	ENST00000573788.5 link	n.492-16912C>T	intron_variant	Intron 3 of 3	4

Frequencies

GnomAD3 genomes

AF:

0.513

AC:

78012

AN:

151970

Hom.:

20472

Cov.:

show subpopulations

Gnomad AFR

AF:

0.591

Gnomad AMI

AF:

0.431

Gnomad AMR

AF:

0.566

Gnomad ASJ

AF:

0.512

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.659

Gnomad FIN

AF:

0.474

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.444

Gnomad OTH

AF:

0.481

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

GnomAD4 genome

AF:

0.513

AC:

78094

AN:

152088

Hom.:

20502

Cov.:

AF XY:

0.519

AC XY:

38566

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.591

AC:

24510

AN:

41478

American (AMR)

AF:

0.566

AC:

8657

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.512

AC:

1776

AN:

3466

East Asian (EAS)

AF:

0.629

AC:

3252

AN:

5172

South Asian (SAS)

AF:

0.658

AC:

3170

AN:

4820

European-Finnish (FIN)

AF:

0.474

AC:

5001

AN:

10560

Middle Eastern (MID)

AF:

0.510

AC:

150

AN:

294

European-Non Finnish (NFE)

AF:

0.444

AC:

30163

AN:

67986

Other (OTH)

AF:

0.483

AC:

1022

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1978

3956

5935

7913

9891

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

694

1388

2082

2776

3470

<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:

0.479

Hom.:

26858

Bravo

AF:

0.522

Asia WGS

AF:

0.683

AC:

2371

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.55

(source)

DANN

Benign

0.70

PhyloP100

-0.69

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over