rs318240759
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PM2PP3_StrongPP5_Very_Strong
The NM_025216.3(WNT10A):c.283G>A(p.Glu95Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a damaging outcome for this variant. Variant has been reported in ClinVar as Likely pathogenic (★★).
Frequency
Consequence
NM_025216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WNT10A | NM_025216.3 | c.283G>A | p.Glu95Lys | missense_variant | 2/4 | ENST00000258411.8 | NP_079492.2 | |
WNT10A | XM_011511929.3 | c.187G>A | p.Glu63Lys | missense_variant | 3/5 | XP_011510231.1 | ||
WNT10A | XM_011511930.2 | c.283G>A | p.Glu95Lys | missense_variant | 2/3 | XP_011510232.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251452Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135914
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461882Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727244
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74290
ClinVar
Submissions by phenotype
not provided Pathogenic:1Other:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2024 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23401279, 22581971, 37361548) - |
not provided, no classification provided | literature only | UniProtKB/Swiss-Prot | - | - - |
Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 17, 2023 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 95 of the WNT10A protein (p.Glu95Lys). This variant is present in population databases (rs318240759, gnomAD 0.003%). This missense change has been observed in individual(s) with autosomal recessive WNT10A-related conditions (PMID: 22581971, 23401279; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 68843). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt WNT10A protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. - |
Tooth agenesis, selective, 4 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 01, 2012 | - - |
SchC6pf-Schulz-Passarge syndrome Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
WNT10A-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 02, 2023 | The WNT10A c.283G>A variant is predicted to result in the amino acid substitution p.Glu95Lys. This variant has been reported in the compound heterozygous and homozygous states in individuals with isolated tooth agenesis or with clinical features of ectodermal dysplasia (Proband 8, van den Boogaard et al. 2012. PubMed ID: 22581971; Patient 11, Plaisancié et al. 2013. PubMed ID: 23401279). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-219747052-G-A). Although we suspect that this variant may be pathogenic, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at