rs199524

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_030753.5(WNT3):​c.323-1024C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.628 in 152,138 control chromosomes in the GnomAD database, including 32,545 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 0.63 ( 32545 hom., cov: 34)

Consequence

WNT3
NM_030753.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.476
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BA1
GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.798 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WNT3NM_030753.5 linkc.323-1024C>A intron_variant ENST00000225512.6 NP_110380.1 P56703
LRRC37A2XM_024450773.2 linkc.4809+220553G>T intron_variant XP_024306541.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WNT3ENST00000225512.6 linkc.323-1024C>A intron_variant 1 NM_030753.5 ENSP00000225512.5 P56703

Frequencies

GnomAD3 genomes
AF:
0.628
AC:
95502
AN:
152020
Hom.:
32544
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.374
Gnomad AMI
AF:
0.666
Gnomad AMR
AF:
0.565
Gnomad ASJ
AF:
0.679
Gnomad EAS
AF:
0.399
Gnomad SAS
AF:
0.819
Gnomad FIN
AF:
0.856
Gnomad MID
AF:
0.639
Gnomad NFE
AF:
0.762
Gnomad OTH
AF:
0.636
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.628
AC:
95530
AN:
152138
Hom.:
32545
Cov.:
34
AF XY:
0.634
AC XY:
47165
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.373
Gnomad4 AMR
AF:
0.565
Gnomad4 ASJ
AF:
0.679
Gnomad4 EAS
AF:
0.399
Gnomad4 SAS
AF:
0.820
Gnomad4 FIN
AF:
0.856
Gnomad4 NFE
AF:
0.762
Gnomad4 OTH
AF:
0.638
Alfa
AF:
0.733
Hom.:
19592
Bravo
AF:
0.584
Asia WGS
AF:
0.605
AC:
2106
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
7.5
DANN
Benign
0.69
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs199524; hg19: chr17-44848438; API