17-46851694-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_003396.3(WNT9B):​c.56C>T​(p.Ala19Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000611 in 1,309,526 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000052 ( 0 hom. )

Consequence

WNT9B
NM_003396.3 missense

Scores

2
1
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.335
Variant links:
Genes affected
WNT9B (HGNC:12779): (Wnt family member 9B) The WNT gene family consists of structurally related genes that 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. Study of its expression in the teratocarcinoma cell line NT2 suggests that it may be implicated in the early process of neuronal differentiation of NT2 cells induced by retinoic acid. This gene is clustered with WNT3, another family member, in the chromosome 17q21 region. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2016]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.31536108).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WNT9BNM_003396.3 linkc.56C>T p.Ala19Val missense_variant Exon 1 of 4 ENST00000290015.7 NP_003387.1 O14905
WNT9BNM_001320458.2 linkc.56C>T p.Ala19Val missense_variant Exon 1 of 5 NP_001307387.1 E7EPC3
LRRC37A2XM_024450773.2 linkc.4810-197362C>T intron_variant Intron 10 of 10 XP_024306541.1
WNT9BXM_011525178.3 linkc.95+18254C>T intron_variant Intron 1 of 3 XP_011523480.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WNT9BENST00000290015.7 linkc.56C>T p.Ala19Val missense_variant Exon 1 of 4 1 NM_003396.3 ENSP00000290015.2 O14905
WNT9BENST00000393461.2 linkc.56C>T p.Ala19Val missense_variant Exon 1 of 5 2 ENSP00000377105.2 E7EPC3
WNT9BENST00000575372.5 linkc.95+18254C>T intron_variant Intron 1 of 2 4 ENSP00000458192.1 I3L0L8

Frequencies

GnomAD3 genomes
AF:
0.0000133
AC:
2
AN:
150870
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000487
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000518
AC:
6
AN:
1158656
Hom.:
0
Cov.:
31
AF XY:
0.00000891
AC XY:
5
AN XY:
561104
show subpopulations
Gnomad4 AFR exome
AF:
0.0000849
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.0000624
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000310
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000133
AC:
2
AN:
150870
Hom.:
0
Cov.:
31
AF XY:
0.0000136
AC XY:
1
AN XY:
73634
show subpopulations
Gnomad4 AFR
AF:
0.0000487
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Inborn genetic diseases Uncertain:1
Jan 19, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.56C>T (p.A19V) alteration is located in exon 1 (coding exon 1) of the WNT9B gene. This alteration results from a C to T substitution at nucleotide position 56, causing the alanine (A) at amino acid position 19 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.060
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
19
DANN
Uncertain
1.0
DEOGEN2
Benign
0.24
T;.
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.18
FATHMM_MKL
Benign
0.65
D
M_CAP
Pathogenic
0.76
D
MetaRNN
Benign
0.32
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
0.34
N;.
PrimateAI
Pathogenic
0.84
D
PROVEAN
Benign
-0.84
N;N
REVEL
Benign
0.21
Sift
Benign
0.28
T;T
Sift4G
Benign
0.36
T;T
Polyphen
0.020
B;B
Vest4
0.22
MutPred
0.48
Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);
MVP
0.75
MPC
0.26
ClinPred
0.63
D
GERP RS
4.2
Varity_R
0.14
gMVP
0.38

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: rs2084848517; hg19: chr17-44929060; API