Variant chr1-227924197-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_003395.4(WNT9A):c.556C>T(p.Arg186Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000248 in 1,493,910 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00058 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00021 ( 3 hom. )

Consequence

WNT9A
NM_003395.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.76

Variant links:

Genes affected

WNT9A (HGNC:12778): (Wnt family member 9A) 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. It is expressed in gastric cancer cell lines. The protein encoded by this gene shows 75% amino acid identity to chicken Wnt14, which has been shown to play a central role in initiating synovial joint formation in the chick limb. This gene is clustered with another family member, WNT3A, in the chromosome 1q42 region. [provided by RefSeq, Jul 2008]

WNT9A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05074793).

BS2

High AC in GnomAd4 at 85 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT9A	NM_003395.4 linkuse as main transcript	c.556C>T	p.Arg186Trp	missense_variant	3/4	ENST00000272164.6
WNT9A	XM_011544271.3 linkuse as main transcript	c.346C>T	p.Arg116Trp	missense_variant	3/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT9A	ENST00000272164.6 linkuse as main transcript	c.556C>T	p.Arg186Trp	missense_variant	3/4	1	NM_003395.4	P1

Frequencies

GnomAD3 genomes

AF:

0.000579

AC:

AN:

146766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00156

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000547

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00205

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000451

Gnomad OTH

AF:

0.000983

GnomAD3 exomes

AF:

0.000398

AC:

100

AN:

251138

Hom.:

AF XY:

0.000420

AC XY:

AN XY:

135806

show subpopulations

Gnomad AFR exome

AF:

0.00191

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000212

AC:

286

AN:

1347006

Hom.:

Cov.:

AF XY:

0.000239

AC XY:

160

AN XY:

668774

show subpopulations

Gnomad4 AFR exome

AF:

0.00205

Gnomad4 AMR exome

AF:

0.000122

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000200

Gnomad4 SAS exome

AF:

0.00174

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000347

Gnomad4 OTH exome

AF:

0.000551

GnomAD4 genome

AF:

0.000579

AC:

AN:

146904

Hom.:

Cov.:

AF XY:

0.000588

AC XY:

AN XY:

71456

show subpopulations

Gnomad4 AFR

AF:

0.00156

Gnomad4 AMR

AF:

0.000546

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00205

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000451

Gnomad4 OTH

AF:

0.000974

Alfa

AF:

0.0000713

Hom.:

Bravo

AF:

0.000491

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000404

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 16, 2024

The c.556C>T (p.R186W) alteration is located in exon 3 (coding exon 3) of the WNT9A gene. This alteration results from a C to T substitution at nucleotide position 556, causing the arginine (R) at amino acid position 186 to be replaced by a tryptophan (W). 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

Uncertain

0.36

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Pathogenic

0.90

Eigen

Benign

0.022

Eigen_PC

Benign

-0.072

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.96

M_CAP

Uncertain

0.29

MetaRNN

Benign

0.051

MetaSVM

Benign

-0.44

MutationAssessor

Uncertain

2.5

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.71

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.48

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

0.98

Vest4

0.52

MVP

0.55

MPC

0.89

ClinPred

0.12

GERP RS

1.0

Varity_R

0.58

gMVP

0.53

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