NM_030753.5:c.81-11338T>C

Variant names:

• chr17-46785247-A-G
• rs199501
• NM_030753.5:c.81-11338T>C

Variant summary

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

The NM_030753.5(WNT3):​c.81-11338T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.639 in 152,020 control chromosomes in the GnomAD database, including 33,525 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 0.64 (33525 hom., cov: 31)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 40 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.815 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.81-11338T>C		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.81-11338T>C		intron	N/A	ENSP00000225512.5	P56703
	WNT3	ENST00000867601.1		c.81-11338T>C		intron	N/A	ENSP00000537660.1
	WNT3	ENST00000931041.1		c.81-11338T>C		intron	N/A	ENSP00000601100.1

Frequencies

GnomAD3 genomes AF: 0.639 AC: 97093 AN: 151904 Hom.: 33524 Cov.: 31

Gnomad AFR AF: 0.381

Gnomad AMI AF: 0.738

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.692

Gnomad EAS AF: 0.503

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.874

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.767

Gnomad OTH AF: 0.644

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

GnomAD4 genome AF: 0.639 AC: 97120 AN: 152020 Hom.: 33525 Cov.: 31 AF XY: 0.647 AC XY: 48064 AN XY: 74316

African (AFR) AF: 0.381 AC: 15782 AN: 41446

American (AMR) AF: 0.569 AC: 8694 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.692 AC: 2400 AN: 3468

East Asian (EAS) AF: 0.504 AC: 2584 AN: 5130

South Asian (SAS) AF: 0.836 AC: 4033 AN: 4822

European-Finnish (FIN) AF: 0.874 AC: 9252 AN: 10590

Middle Eastern (MID) AF: 0.653 AC: 192 AN: 294

European-Non Finnish (NFE) AF: 0.767 AC: 52146 AN: 67970

Other (OTH) AF: 0.646 AC: 1365 AN: 2114

Alfa AF: 0.711 Hom.: 156010

Bravo AF: 0.596

Asia WGS AF: 0.639 AC: 2223 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	3.2
DANN	Benign	0.61
PhyloP100		-0.14
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: rs199501; hg19: chr17-44862613;