rs199524

Variant names:

• chr17-46771072-G-T
• rs199524
• NM_030753.5:c.323-1024C>A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.476
• Publications: 30 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=-0.79).
• 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

Sel.	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	P56703

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	ENST00000225512.6	TSL:1 MANE Select	c.323-1024C>A		intron	N/A	ENSP00000225512.5	P56703
	WNT3	ENST00000867601.1		c.323-1024C>A		intron	N/A	ENSP00000537660.1
	WNT3	ENST00000931041.1		c.323-1024C>A		intron	N/A	ENSP00000601100.1

Frequencies

GnomAD3 genomes AF: 0.628 AC: 95502 AN: 152020 Hom.: 32544 Cov.: 34

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.: 34 AF XY: 0.634 AC XY: 47165 AN XY: 74388

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

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
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)

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: rs199524; hg19: chr17-44848438;