ClinVar Miner

Submissions for variant NM_144991.3(TSPEAR):c.1247A>C (p.Tyr416Ser)

gnomAD frequency: 0.00008  dbSNP: rs781913166
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001800031 SCV002044107 likely pathogenic not provided 2023-10-05 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001800031 SCV003267390 uncertain significance not provided 2023-05-02 criteria provided, single submitter clinical testing 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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on TSPEAR protein function. ClinVar contains an entry for this variant (Variation ID: 1329723). This missense change has been observed in individual(s) with ectodermal dysplasia (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs781913166, gnomAD 0.01%). This sequence change replaces tyrosine, which is neutral and polar, with serine, which is neutral and polar, at codon 416 of the TSPEAR protein (p.Tyr416Ser).
Ambry Genetics RCV002544371 SCV003684385 uncertain significance Inborn genetic diseases 2021-09-16 criteria provided, single submitter clinical testing The c.1247A>C (p.Y416S) alteration is located in exon 8 (coding exon 8) of the TSPEAR gene. This alteration results from a A to C substitution at nucleotide position 1247, causing the tyrosine (Y) at amino acid position 416 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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