17-46779275-G-C

Variant names:

• chr17-46779275-G-C
• rs199515
• NM_030753.5:c.81-5366C>G

Variant summary

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

The NM_030753.5(WNT3):​c.81-5366C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,234 control chromosomes in the GnomAD database, including 54,091 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 0.84 (54091 hom., cov: 33)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.646
• Publications: 76 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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.81-5366C>G		intron	N/A	NP_110380.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT3	ENST00000225512.6	TSL:1 MANE Select	c.81-5366C>G		intron	N/A	ENSP00000225512.5
	WNT3	ENST00000706495.1		c.-115-5366C>G		intron	N/A	ENSP00000516418.1
	WNT3	ENST00000573788.5	TSL:4	n.492-5366C>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.840 AC: 127833 AN: 152116 Hom.: 54030 Cov.: 33

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.739

Gnomad AMR AF: 0.822

Gnomad ASJ AF: 0.743

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.940

Gnomad FIN AF: 0.927

Gnomad MID AF: 0.778

Gnomad NFE AF: 0.795

Gnomad OTH AF: 0.812

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

GnomAD4 genome AF: 0.841 AC: 127956 AN: 152234 Hom.: 54091 Cov.: 33 AF XY: 0.849 AC XY: 63223 AN XY: 74430

African (AFR) AF: 0.880 AC: 36557 AN: 41526

American (AMR) AF: 0.822 AC: 12580 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.743 AC: 2577 AN: 3470

East Asian (EAS) AF: 0.999 AC: 5181 AN: 5186

South Asian (SAS) AF: 0.941 AC: 4544 AN: 4830

European-Finnish (FIN) AF: 0.927 AC: 9839 AN: 10610

Middle Eastern (MID) AF: 0.779 AC: 229 AN: 294

European-Non Finnish (NFE) AF: 0.795 AC: 54058 AN: 67998

Other (OTH) AF: 0.815 AC: 1717 AN: 2108

Alfa AF: 0.829 Hom.: 6528

Bravo AF: 0.832

Asia WGS AF: 0.968 AC: 3366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	11
DANN	Benign	0.72
PhyloP100		0.65
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: rs199515; hg19: chr17-44856641;