17-46872756-T-C

Position:

chr17-46872756-T-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003396.3(WNT9B):c.317T>C(p.Met106Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.74 in 1,590,790 control chromosomes in the GnomAD database, including 434,800 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.78 ( 45843 hom., cov: 26)

Exomes 𝑓: 0.74 ( 388957 hom. )

Consequence

WNT9B
NM_003396.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.834

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=7.5856167E-7).

BP6

Variant 17-46872756-T-C is Benign according to our data. Variant chr17-46872756-T-C is described in ClinVar as [Benign]. Clinvar id is 1598959.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT9B	NM_003396.3 linkuse as main transcript	c.317T>C	p.Met106Thr	missense_variant	2/4	ENST00000290015.7	NP_003387.1	O14905
WNT9B	NM_001320458.2 linkuse as main transcript	c.317T>C	p.Met106Thr	missense_variant	2/5		NP_001307387.1	E7EPC3
WNT9B	XM_011525178.3 linkuse as main transcript	c.335T>C	p.Met112Thr	missense_variant	2/4		XP_011523480.1
LRRC37A2	XM_024450773.2 linkuse as main transcript	c.4810-176300T>C		intron_variant			XP_024306541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
WNT9B	ENST00000290015.7 linkuse as main transcript	c.317T>C	p.Met106Thr	missense_variant	2/4	1	NM_003396.3	ENSP00000290015.2	O14905
WNT9B	ENST00000393461.2 linkuse as main transcript	c.317T>C	p.Met106Thr	missense_variant	2/5	2		ENSP00000377105.2	E7EPC3
WNT9B	ENST00000575372.5 linkuse as main transcript	c.335T>C	p.Met112Thr	missense_variant	2/3	4		ENSP00000458192.1	I3L0L8

Frequencies

GnomAD3 genomes

AF:

0.779

AC:

116673

AN:

149756

Hom.:

45800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.906

Gnomad AMI

AF:

0.817

Gnomad AMR

AF:

0.712

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.488

Gnomad SAS

AF:

0.702

Gnomad FIN

AF:

0.787

Gnomad MID

AF:

0.831

Gnomad NFE

AF:

0.747

Gnomad OTH

AF:

0.787

GnomAD3 exomes

AF:

0.705

AC:

168856

AN:

239642

Hom.:

60833

AF XY:

0.708

AC XY:

92586

AN XY:

130756

show subpopulations

Gnomad AFR exome

AF:

0.907

Gnomad AMR exome

AF:

0.614

Gnomad ASJ exome

AF:

0.652

Gnomad EAS exome

AF:

0.442

Gnomad SAS exome

AF:

0.690

Gnomad FIN exome

AF:

0.767

Gnomad NFE exome

AF:

0.743

Gnomad OTH exome

AF:

0.721

GnomAD4 exome

AF:

0.736

AC:

1060645

AN:

1440920

Hom.:

388957

Cov.:

AF XY:

0.735

AC XY:

526634

AN XY:

716286

show subpopulations

Gnomad4 AFR exome

AF:

0.911

Gnomad4 AMR exome

AF:

0.633

Gnomad4 ASJ exome

AF:

0.673

Gnomad4 EAS exome

AF:

0.538

Gnomad4 SAS exome

AF:

0.694

Gnomad4 FIN exome

AF:

0.776

Gnomad4 NFE exome

AF:

0.744

Gnomad4 OTH exome

AF:

0.729

GnomAD4 genome

AF:

0.779

AC:

116766

AN:

149870

Hom.:

45843

Cov.:

AF XY:

0.778

AC XY:

56893

AN XY:

73086

show subpopulations

Gnomad4 AFR

AF:

0.906

Gnomad4 AMR

AF:

0.712

Gnomad4 ASJ

AF:

0.655

Gnomad4 EAS

AF:

0.488

Gnomad4 SAS

AF:

0.702

Gnomad4 FIN

AF:

0.787

Gnomad4 NFE

AF:

0.747

Gnomad4 OTH

AF:

0.784

Alfa

AF:

0.735

Hom.:

38719

Bravo

AF:

0.769

TwinsUK

AF:

0.737

AC:

2732

ALSPAC

AF:

0.737

AC:

2842

ESP6500AA

AF:

0.905

AC:

3968

ESP6500EA

AF:

0.733

AC:

6275

ExAC

AF:

0.710

AC:

85898

Asia WGS

AF:

0.585

AC:

2036

AN:

3478

EpiCase

AF:

0.743

EpiControl

AF:

0.743

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

WNT9B-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.052

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

2.4

DANN

Benign

0.33

DEOGEN2

Benign

0.35

.;T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.0083

MetaRNN

Benign

7.6e-7

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.90

.;N;.

PrimateAI

Benign

0.48

PROVEAN

Benign

0.85

.;N;N

REVEL

Benign

0.14

Sift

Benign

0.63

.;T;T

Sift4G

Benign

0.39

T;T;T

Polyphen

0.0

.;B;B

Vest4

0.034, 0.023

MPC

0.30

ClinPred

0.0084

GERP RS

-0.034

Varity_R

0.071

gMVP

0.26

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