NM_025216.3:c.208C>T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_025216.3(WNT10A):c.208C>T(p.Arg70Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00136 in 1,614,174 control chromosomes in the GnomAD database, including 8 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
Consequence
NM_025216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WNT10A | NM_025216.3 | c.208C>T | p.Arg70Trp | missense_variant | Exon 2 of 4 | ENST00000258411.8 | NP_079492.2 | |
WNT10A | XM_011511929.3 | c.112C>T | p.Arg38Trp | missense_variant | Exon 3 of 5 | XP_011510231.1 | ||
WNT10A | XM_011511930.2 | c.208C>T | p.Arg70Trp | missense_variant | Exon 2 of 3 | XP_011510232.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00112 AC: 171AN: 152176Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.00177 AC: 444AN: 251386Hom.: 2 AF XY: 0.00206 AC XY: 280AN XY: 135880
GnomAD4 exome AF: 0.00139 AC: 2028AN: 1461882Hom.: 7 Cov.: 32 AF XY: 0.00154 AC XY: 1120AN XY: 727246
GnomAD4 genome AF: 0.00111 AC: 169AN: 152292Hom.: 1 Cov.: 32 AF XY: 0.00107 AC XY: 80AN XY: 74470
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Observed in the heterozygous state in two brothers with tooth agenesis; the more severely affected brother was also heterozygous for an EDARADD variant (PMID: 23991204); Identified in an individual with hypodontia; this individual's mother also harbors the variant and has fully developed dentition (PMID: 35999385); Reported along with a second WNT10A variant in a patient with oligodontia, but familial segregation information was not included (PMID: 24449199); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 24449199, 35999385, 23991204) -
WNT10A: BS2 -
SchC6pf-Schulz-Passarge syndrome Benign:2
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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
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. -
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WNT10A-related disorder Uncertain:1
The WNT10A c.208C>T variant is predicted to result in the amino acid substitution p.Arg70Trp. This variant has been reported in the heterozygous state in two brothers with missing permanent teeth, and one of the two brothers has more severe phenotype also carried a truncating variant in the EDARADD gene (Arte et al. 2013. PubMed ID: 23991204). This variant is documented in 0.59% of alleles in individuals of South Asian descent in gnomAD. This variant could be benign. At this time, the clinical significance of this variant is uncertain due to insufficient functional and genetic evidence. -
Odonto-onycho-dermal dysplasia;C1835492:Tooth agenesis, selective, 4 Benign:1
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Tooth agenesis, selective, 4 Benign:1
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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at