rs12452064

Variant names:

• chr17-46790821-G-A
• rs12452064
• NM_030753.5:c.81-16912C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-46790821-G-A
• chr17-46790821-G-C
• chr17-46790821-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.688
• Publications: 21 publications found

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]

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]

ACMG classification

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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	NM_030753.5	MANE Select	c.81-16912C>T		intron	N/A	NP_110380.1	P56703

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	ENST00000225512.6	TSL:1 MANE Select	c.81-16912C>T		intron	N/A	ENSP00000225512.5	P56703
	WNT3	ENST00000867601.1		c.81-16912C>T		intron	N/A	ENSP00000537660.1
	WNT3	ENST00000931041.1		c.81-16912C>T		intron	N/A	ENSP00000601100.1

Frequencies

GnomAD3 genomes AF: 0.513 AC: 78012 AN: 151970 Hom.: 20472 Cov.: 33

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.: 33 AF XY: 0.519 AC XY: 38566 AN XY: 74346

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.55
DANN	Benign	0.70
PhyloP100		-0.69
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12452064; hg19: chr17-44868187;