ClinVar Miner

Submissions for variant NM_030761.5(WNT4):c.697G>A (p.Ala233Thr)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics, Fulgent Genetics RCV005015413 SCV005645906 likely benign Mullerian aplasia and hyperandrogenism; SERKAL syndrome 2024-03-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005112638 SCV005730502 uncertain significance not provided 2024-05-27 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 233 of the WNT4 protein (p.Ala233Thr). This variant is present in population databases (rs41441349, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with primary amenorrhea and hyperandrogenism (PMID: 21377155). 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 not expected to disrupt WNT4 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects WNT4 function (PMID: 21377155). 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.

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