NM_030753.5:c.81-15452C>T

Variant names:

• chr17-46789361-G-A
• rs199496
• NM_030753.5:c.81-15452C>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.81-15452C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.105 in 152,202 control chromosomes in the GnomAD database, including 974 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 0.11 (974 hom., cov: 32)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.791
• Publications: 10 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.159 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.81-15452C>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.81-15452C>T		intron	N/A	ENSP00000225512.5
	WNT3	ENST00000706495.1		c.-115-15452C>T		intron	N/A	ENSP00000516418.1
	WNT3	ENST00000573788.5	TSL:4	n.492-15452C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15996 AN: 152084 Hom.: 972 Cov.: 32

Gnomad AFR AF: 0.162

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0720

Gnomad ASJ AF: 0.0953

Gnomad EAS AF: 0.0235

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0931

Gnomad OTH AF: 0.112

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

GnomAD4 genome AF: 0.105 AC: 16016 AN: 152202 Hom.: 974 Cov.: 32 AF XY: 0.102 AC XY: 7625 AN XY: 74422

African (AFR) AF: 0.162 AC: 6720 AN: 41522

American (AMR) AF: 0.0718 AC: 1098 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0953 AC: 330 AN: 3462

East Asian (EAS) AF: 0.0236 AC: 122 AN: 5180

South Asian (SAS) AF: 0.0249 AC: 120 AN: 4818

European-Finnish (FIN) AF: 0.0884 AC: 938 AN: 10612

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.0930 AC: 6328 AN: 68008

Other (OTH) AF: 0.113 AC: 239 AN: 2112

Alfa AF: 0.0953 Hom.: 1145

Bravo AF: 0.105

Asia WGS AF: 0.0380 AC: 132 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.75
DANN	Benign	0.38
PhyloP100		-0.79
Mutation Taster		=99/1	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: rs199496; hg19: chr17-44866727;