Variant 17-46872759-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000290015.7(WNT9B):c.320G>T(p.Gly107Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,122 control chromosomes in the GnomAD database, with no homozygous occurrence. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

WNT9B
ENST00000290015.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

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:):

LRRC37A2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
WNT9B	NM_003396.3 linkuse as main transcript	c.320G>T	p.Gly107Val	missense_variant	2/4	ENST00000290015.7	NP_003387.1
WNT9B	NM_001320458.2 linkuse as main transcript	c.320G>T	p.Gly107Val	missense_variant	2/5		NP_001307387.1
WNT9B	XM_011525178.3 linkuse as main transcript	c.338G>T	p.Gly113Val	missense_variant	2/4		XP_011523480.1
LRRC37A2	XM_024450773.2 linkuse as main transcript	c.4810-176297G>T		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
WNT9B	ENST00000290015.7 linkuse as main transcript	c.320G>T	p.Gly107Val	missense_variant	2/4	1	NM_003396.3	ENSP00000290015	P1
WNT9B	ENST00000393461.2 linkuse as main transcript	c.320G>T	p.Gly107Val	missense_variant	2/5	2		ENSP00000377105
WNT9B	ENST00000575372.5 linkuse as main transcript	c.338G>T	p.Gly113Val	missense_variant	2/3	4		ENSP00000458192

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.88e-7

AC:

AN:

1454122

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723136

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 12, 2023

The c.320G>T (p.G107V) alteration is located in exon 2 (coding exon 2) of the WNT9B gene. This alteration results from a G to T substitution at nucleotide position 320, causing the glycine (G) at amino acid position 107 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

0.16

BayesDel_addAF

Benign

-0.026

BayesDel_noAF

Benign

-0.28

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Uncertain

0.46

.;T;.

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.92

M_CAP

Benign

0.055

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.0

.;N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.4

.;N;N

REVEL

Benign

0.23

Sift

Benign

0.14

.;T;T

Sift4G

Uncertain

0.060

T;T;T

Polyphen

0.025, 0.68

.;B;P

Vest4

0.43, 0.44

MutPred

0.48

.;Loss of helix (P = 0.0626);Loss of helix (P = 0.0626);

MVP

0.83

MPC

0.48

ClinPred

0.35

GERP RS

2.3

Varity_R

0.15

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