rs77583146
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2
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). Synonymous variant affecting the same amino acid position (i.e. G165G) has been classified as Likely benign.
Frequency
Consequence
NM_025216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
WNT10A | NM_025216.3 | c.493G>A | p.Gly165Arg | missense_variant | 3/4 | ENST00000258411.8 | |
WNT10A | XM_011511929.3 | c.397G>A | p.Gly133Arg | missense_variant | 4/5 | ||
WNT10A | XM_011511930.2 | c.377-2674G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
WNT10A | ENST00000258411.8 | c.493G>A | p.Gly165Arg | missense_variant | 3/4 | 1 | NM_025216.3 | P1 | |
WNT10A | ENST00000458582.1 | c.264-2674G>A | intron_variant | 3 | |||||
WNT10A | ENST00000483911.1 | downstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00718 AC: 1093AN: 152240Hom.: 4 Cov.: 33
GnomAD3 exomes AF: 0.00685 AC: 1722AN: 251334Hom.: 11 AF XY: 0.00669 AC XY: 909AN XY: 135888
GnomAD4 exome AF: 0.0106 AC: 15516AN: 1461826Hom.: 104 Cov.: 32 AF XY: 0.0104 AC XY: 7541AN XY: 727220
GnomAD4 genome ? AF: 0.00717 AC: 1093AN: 152358Hom.: 4 Cov.: 33 AF XY: 0.00659 AC XY: 491AN XY: 74504
ClinVar
Submissions by phenotype
SchC6pf-Schulz-Passarge syndrome Uncertain:1Benign:2
Benign, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 30, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 08, 2023 | Observed in the heterozygous state or as compound heterozygous with another variant in the WNT10A gene in both individuals with oligodontia as well as in unaffected individuals, and was reported as a polymorphism (Bohring et al., 2009; Yang et al., 2015; Mostowska et al., 2015); Observed in individuals with tooth agenesis in published literature who had variants in other genes associated with ectodermal anomalies (Arte et al., 2013); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33311554, 19559398, 25545742, 30426266, 23991204, 25629078, 30555066, 31798653, 36250548) - |
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | WNT10A: BS1, BS2 - |
Tooth agenesis, selective, 4 Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jul 22, 2021 | - - |
Odonto-onycho-dermal dysplasia Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Jun 10, 2021 | - - |
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Tooth agenesis Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | Yale Center for Mendelian Genomics, Yale University | Sep 15, 2014 | - - |
WNT10A-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 18, 2020 | 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
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at