rs974508350

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000258411.8(WNT10A):ā€‹c.959C>Gā€‹(p.Pro320Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000658 in 152,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P320S) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

WNT10A
ENST00000258411.8 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.51
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.25521004).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WNT10ANM_025216.3 linkuse as main transcriptc.959C>G p.Pro320Arg missense_variant 4/4 ENST00000258411.8 NP_079492.2
WNT10AXM_011511929.3 linkuse as main transcriptc.863C>G p.Pro288Arg missense_variant 5/5 XP_011510231.1
WNT10AXM_011511930.2 linkuse as main transcriptc.579C>G p.Ala193= synonymous_variant 3/3 XP_011510232.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WNT10AENST00000258411.8 linkuse as main transcriptc.959C>G p.Pro320Arg missense_variant 4/41 NM_025216.3 ENSP00000258411 P1
WNT10AENST00000458582.1 linkuse as main transcriptc.468C>G p.Ala156= synonymous_variant 2/23 ENSP00000388812

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152036
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
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
Cov.:
31
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
152036
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74262
show subpopulations
Gnomad4 AFR
AF:
0.0000241
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:
0.00000756

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpSep 01, 2021This sequence change replaces proline with arginine at codon 320 of the WNT10A protein (p.Pro320Arg). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with WNT10A-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.086
BayesDel_addAF
Benign
-0.027
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
20
DANN
Benign
0.85
DEOGEN2
Benign
0.16
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.21
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.56
T
M_CAP
Uncertain
0.25
D
MetaRNN
Benign
0.26
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.20
N
MutationTaster
Benign
0.76
D
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
0.60
N
REVEL
Benign
0.17
Sift
Benign
0.51
T
Sift4G
Benign
0.60
T
Polyphen
0.35
B
Vest4
0.39
MutPred
0.41
Gain of methylation at P320 (P = 0.0081);
MVP
0.81
MPC
1.1
ClinPred
0.27
T
GERP RS
3.7
Varity_R
0.080
gMVP
0.44

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.

Other links and lift over

dbSNP: rs974508350; hg19: chr2-219757698; API