NM_025216.3:c.493G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_025216.3(WNT10A):c.493G>A(p.Gly165Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0103 in 1,614,184 control chromosomes in the GnomAD database, including 108 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0072 ( 4 hom., cov: 33)

Exomes 𝑓: 0.011 ( 104 hom. )

Consequence

WNT10A
NM_025216.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:8

Conservation

PhyloP100: 7.87

Variant links:

Genes affected

WNT10A (HGNC:13829): (Wnt family member 10A) The WNT gene family consists of structurally related genes which 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 strongly expressed in the cell lines of promyelocytic leukemia and Burkitt's lymphoma. In addition, it and another family member, the WNT6 gene, are strongly coexpressed in colorectal cancer cell lines. The gene overexpression may play key roles in carcinogenesis through activation of the WNT-beta-catenin-TCF signaling pathway. This gene and the WNT6 gene are clustered in the chromosome 2q35 region. [provided by RefSeq, Jul 2008]

WNT10A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012216538).

BP6

Variant 2-218890100-G-A is Benign according to our data. Variant chr2-218890100-G-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 334399.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=2, Benign=4, Uncertain_significance=3}. Variant chr2-218890100-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00717 (1093/152358) while in subpopulation NFE AF= 0.0122 (830/68036). AF 95% confidence interval is 0.0115. There are 4 homozygotes in gnomad4. There are 491 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT10A	NM_025216.3 link	c.493G>A	p.Gly165Arg	missense_variant	Exon 3 of 4	ENST00000258411.8	NP_079492.2	Q9GZT5A0A2K8FR47
WNT10A	XM_011511929.3 link	c.397G>A	p.Gly133Arg	missense_variant	Exon 4 of 5		XP_011510231.1
WNT10A	XM_011511930.2 link	c.377-2674G>A		intron_variant	Intron 2 of 2		XP_011510232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WNT10A	ENST00000258411.8 link	c.493G>A	p.Gly165Arg	missense_variant	Exon 3 of 4	1	NM_025216.3	ENSP00000258411.3	Q9GZT5
WNT10A	ENST00000458582.1 link	c.263-2674G>A		intron_variant	Intron 1 of 1	3		ENSP00000388812.1	H7BZB8
WNT10A	ENST00000483911.1 link	n.*1G>A		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.00718

AC:

1093

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00191

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.00281

Gnomad ASJ

AF:

0.00288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00838

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0122

Gnomad OTH

AF:

0.00764

GnomAD3 exomes

AF:

0.00685

AC:

1722

AN:

251334

Hom.:

AF XY:

0.00669

AC XY:

909

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00237

Gnomad ASJ exome

AF:

0.00288

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00949

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00636

GnomAD4 exome

AF:

0.0106

AC:

15516

AN:

1461826

Hom.:

104

Cov.:

AF XY:

0.0104

AC XY:

7541

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00143

Gnomad4 AMR exome

AF:

0.00242

Gnomad4 ASJ exome

AF:

0.00237

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0105

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.00945

GnomAD4 genome

AF:

0.00717

AC:

1093

AN:

152358

Hom.:

Cov.:

AF XY:

0.00659

AC XY:

491

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00190

Gnomad4 AMR

AF:

0.00281

Gnomad4 ASJ

AF:

0.00288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00838

Gnomad4 NFE

AF:

0.0122

Gnomad4 OTH

AF:

0.00756

Alfa

AF:

0.00980

Hom.:

Bravo

AF:

0.00669

TwinsUK

AF:

0.0119

AC:

ALSPAC

AF:

0.0130

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.0107

AC:

ExAC

AF:

0.00731

AC:

888

EpiCase

AF:

0.00943

EpiControl

AF:

0.00978

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:8

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

SchC6pf-Schulz-Passarge syndrome

Uncertain:1Benign:2

Jul 22, 2021

Genome-Nilou Lab

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Dec 30, 2019

Natera, Inc.

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Uncertain:1Benign:1

Dec 10, 2024

GeneDx

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Observed in the heterozygous state or as compound heterozygous with another variant in the WNT10A gene in both individuals with oligodontia and unaffected individuals, and has been reported as a polymorphism (PMID: 19559398, 25629078, 25545742, 36250548); Observed in individuals with tooth agenesis in the published literature who had variants in other genes associated with ectodermal anomalies (PMID: 23991204); Observed as heterozygous by whole exome sequencing in a patient with short anagen hair (PMID: 37671665); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33311554, 25545742, 25629078, 30426266, 36250548, 31798653, 30555066, 23991204, 19559398, 37671665) -

Oct 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

WNT10A: BS1, BS2 -

Tooth agenesis, selective, 4

Uncertain:1Benign:1

Jul 22, 2021

Genome-Nilou Lab

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. -

Odonto-onycho-dermal dysplasia

Benign:2

Jun 10, 2021

Genome-Nilou Lab

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Tooth agenesis

Uncertain:1

Sep 15, 2014

Yale Center for Mendelian Genomics, Yale University

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: literature only

- -

WNT10A-related disorder

Benign:1

Dec 18, 2020

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4

Benign:1

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.34

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.57

Eigen

Benign

0.17

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.37

MutationAssessor

Uncertain

2.2

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.9

REVEL

Uncertain

0.35

Sift

Benign

0.032

Sift4G

Benign

0.24

Polyphen

0.11

Vest4

0.83

MutPred

0.49

Loss of helix (P = 0.028);

MVP

0.86

MPC

0.46

ClinPred

0.030

GERP RS

4.5

Varity_R

0.18

gMVP

0.80

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