17-46851694-C-T

Variant names:

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

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]

WNT9B links:

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]

LRRC37A2 links:

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
WNT9B	NM_003396.3 link	c.56C>T	p.Ala19Val	missense_variant	Exon 1 of 4	ENST00000290015.7	NP_003387.1	O14905
WNT9B	NM_001320458.2 link	c.56C>T	p.Ala19Val	missense_variant	Exon 1 of 5		NP_001307387.1	E7EPC3
LRRC37A2	XM_024450773.2 link	c.4810-197362C>T		intron_variant	Intron 10 of 10		XP_024306541.1
WNT9B	XM_011525178.3 link	c.95+18254C>T		intron_variant	Intron 1 of 3		XP_011523480.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT9B	ENST00000290015.7 link	c.56C>T	p.Ala19Val	missense_variant	Exon 1 of 4	1	NM_003396.3	ENSP00000290015.2	O14905
WNT9B	ENST00000393461.2 link	c.56C>T	p.Ala19Val	missense_variant	Exon 1 of 5	2		ENSP00000377105.2	E7EPC3
WNT9B	ENST00000575372.5 link	c.95+18254C>T		intron_variant	Intron 1 of 2	4		ENSP00000458192.1	I3L0L8

Frequencies

GnomAD3 genomes

AF:

0.0000133

AC:

AN:

150870

Hom.:

Cov.:

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:

AN:

1158656

Hom.:

Cov.:

AF XY:

0.00000891

AC XY:

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:

AN:

150870

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

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

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.24

T;.

Eigen

Benign

-0.35

Eigen_PC

Benign

-0.18

FATHMM_MKL

Benign

0.65

M_CAP

Pathogenic

0.76

MetaRNN

Benign

0.32

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.34

N;.

PrimateAI

Pathogenic

0.84

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over