ClinVar Miner

Submissions for variant NM_006846.4(SPINK5):c.1887G>C (p.Lys629Asn)

gnomAD frequency: 0.00004  dbSNP: rs772652367
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000688902 SCV000816529 uncertain significance Netherton syndrome 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 629 of the SPINK5 protein (p.Lys629Asn). This variant also falls at the last nucleotide of exon 20, which is part of the consensus splice site for this exon. This variant is present in population databases (rs772652367, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SPINK5-related conditions. ClinVar contains an entry for this variant (Variation ID: 568516). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus 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.

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