ClinVar Miner

Submissions for variant NM_004568.6(SERPINB6):c.314C>A (p.Ser105Tyr)

gnomAD frequency: 0.00051  dbSNP: rs148530934
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000223127 SCV000272422 uncertain significance not specified 2017-04-13 criteria provided, single submitter clinical testing The p.Ser105Tyr variant in SERPINB6 has been previously reported by our laborato ry in the heterozygous state in two individuals with hearing loss. It has also been identified in 0.1% (102/126684) of European chromosomes by the Genome Aggre gation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs148530934). A lthough this variant has been seen in the general population, its frequency is n ot high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Ser105Tyr variant i s uncertain.
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center RCV001375306 SCV001571928 uncertain significance Usher syndrome 2021-04-12 criteria provided, single submitter clinical testing PM2_Supporting, PP3_Supporting, BP5_Supporting
GeneDx RCV001547089 SCV001766714 likely benign not provided 2020-08-25 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001547089 SCV002182846 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with tyrosine, which is neutral and polar, at codon 105 of the SERPINB6 protein (p.Ser105Tyr). This variant is present in population databases (rs148530934, gnomAD 0.08%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with SERPINB6-related conditions. ClinVar contains an entry for this variant (Variation ID: 229240). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
CeGaT Center for Human Genetics Tuebingen RCV001547089 SCV002497378 uncertain significance not provided 2022-02-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV000223127 SCV003756915 uncertain significance not specified 2024-04-29 criteria provided, single submitter clinical testing The c.314C>A (p.S105Y) alteration is located in exon 4 (coding exon 3) of the SERPINB6 gene. This alteration results from a C to A substitution at nucleotide position 314, causing the serine (S) at amino acid position 105 to be replaced by a tyrosine (Y). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic RCV001547089 SCV004227180 uncertain significance not provided 2023-03-22 criteria provided, single submitter clinical testing BS1_supporting

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