17-46768172-C-T

Variant names:

• chr17-46768172-C-T
• rs77266163
• NM_030753.5:c.*8+140G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030753.5(WNT3):​c.*8+140G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0169 in 1,246,776 control chromosomes in the GnomAD database, including 258 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (20 hom., cov: 32)
  • Exomes 𝑓: 0.017 (238 hom.)
• Consequence: WNT3 NM_030753.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.606
• Publications: 2 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 17-46768172-C-T is Benign according to our data. Variant chr17-46768172-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1318109.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.014 (2140/152316) while in subpopulation NFE AF = 0.0214 (1457/68032). AF 95% confidence interval is 0.0205. There are 20 homozygotes in GnomAd4. There are 1015 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR,Unknown gene

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.*8+140G>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.*8+140G>A		intron	N/A	ENSP00000225512.5	P56703
	WNT3	ENST00000867601.1		c.*148G>A		3_prime_UTR	Exon 4 of 4	ENSP00000537660.1
	WNT3	ENST00000931041.1		c.*8+140G>A		intron	N/A	ENSP00000601100.1

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2140 AN: 152198 Hom.: 20 Cov.: 32

Gnomad AFR AF: 0.00398

Gnomad AMI AF: 0.0581

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00375

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00311

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0214

Gnomad OTH AF: 0.00574

GnomAD4 exome AF: 0.0173 AC: 18967 AN: 1094460 Hom.: 238 AF XY: 0.0171 AC XY: 9352 AN XY: 547720

African (AFR) AF: 0.00274 AC: 70 AN: 25586

American (AMR) AF: 0.00277 AC: 88 AN: 31760

Ashkenazi Jewish (ASJ) AF: 0.00346 AC: 74 AN: 21380

East Asian (EAS) AF: 0.00 AC: 0 AN: 34300

South Asian (SAS) AF: 0.00204 AC: 140 AN: 68714

European-Finnish (FIN) AF: 0.0365 AC: 1254 AN: 34354

Middle Eastern (MID) AF: 0.00263 AC: 9 AN: 3424

European-Non Finnish (NFE) AF: 0.0202 AC: 16674 AN: 827112

Other (OTH) AF: 0.0138 AC: 658 AN: 47830

GnomAD4 genome AF: 0.0140 AC: 2140 AN: 152316 Hom.: 20 Cov.: 32 AF XY: 0.0136 AC XY: 1015 AN XY: 74476

African (AFR) AF: 0.00397 AC: 165 AN: 41574

American (AMR) AF: 0.00464 AC: 71 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00375 AC: 13 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00311 AC: 15 AN: 4824

European-Finnish (FIN) AF: 0.0333 AC: 354 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0214 AC: 1457 AN: 68032

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

Alfa AF: 0.0169 Hom.: 10

Bravo AF: 0.0115

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.82
PhyloP100		0.61
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs77266163; hg19: chr17-44845538;