chr17-46791064-G-A

Variant names:

• chr17-46791064-G-A
• rs199495
• NM_030753.5:c.81-17155C>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.81-17155C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 151,964 control chromosomes in the GnomAD database, including 8,671 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 0.32 (8671 hom., cov: 32)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.428
• Publications: 6 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.412 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.81-17155C>T		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.81-17155C>T		intron	N/A	ENSP00000225512.5
	WNT3	ENST00000706495.1		c.-115-17155C>T		intron	N/A	ENSP00000516418.1
	WNT3	ENST00000573788.5	TSL:4	n.492-17155C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48308 AN: 151846 Hom.: 8666 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.290

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.410

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.416

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.318 AC: 48322 AN: 151964 Hom.: 8671 Cov.: 32 AF XY: 0.317 AC XY: 23537 AN XY: 74260

African (AFR) AF: 0.138 AC: 5721 AN: 41442

American (AMR) AF: 0.290 AC: 4432 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1255 AN: 3472

East Asian (EAS) AF: 0.332 AC: 1713 AN: 5154

South Asian (SAS) AF: 0.304 AC: 1463 AN: 4810

European-Finnish (FIN) AF: 0.410 AC: 4324 AN: 10550

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.416 AC: 28251 AN: 67950

Other (OTH) AF: 0.328 AC: 693 AN: 2110

Alfa AF: 0.381 Hom.: 7061

Bravo AF: 0.306

Asia WGS AF: 0.260 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.34
DANN	Benign	0.63
PhyloP100		-0.43
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: rs199495; hg19: chr17-44868430;