ClinVar Miner

Submissions for variant NM_025216.3(WNT10A):c.427C>T (p.His143Tyr)

gnomAD frequency: 0.00011  dbSNP: rs202024965
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001248684 SCV001422189 uncertain significance Odonto-onycho-dermal dysplasia; Tooth agenesis, selective, 4 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces histidine with tyrosine at codon 143 of the WNT10A protein (p.His143Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine. This variant is present in population databases (rs202024965, ExAC 0.06%). This missense change has been observed in individual(s) with clinical features of ectodermal dysplasia (PMID: 20979233; Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 972612). 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 disruptive. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003323833 SCV004029729 uncertain significance not specified 2023-07-21 criteria provided, single submitter clinical testing Variant summary: WNT10A c.427C>T (p.His143Tyr) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00025 in 251392 control chromosomes, predominantly at a frequency of 0.00036 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than estimated for a pathogenic variant in WNT10A causing Odonto-onycho-dermal dysplasia, allowing no conclusion about variant significance. c.427C>T has been reported in the literature as a non-informative genotype (exact zygosity or genotype not specified) in at least one individual affected with hypohidrotic and anhidrotic ectodermal dysplasia without a reported second variant (e.g. Cluzaeu_2010). These report(s) do not provide unequivocal conclusions about association of the variant with Odonto-onycho-dermal dysplasia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 20979233). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001830048 SCV002078822 uncertain significance SchC6pf-Schulz-Passarge syndrome 2020-01-14 no assertion criteria provided clinical testing

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