ClinVar Miner

Submissions for variant NM_006846.4(SPINK5):c.1660G>A (p.Glu554Lys)

gnomAD frequency: 0.00002  dbSNP: rs374599097
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000816510 SCV000957023 uncertain significance Netherton syndrome 2022-08-01 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 554 of the SPINK5 protein (p.Glu554Lys). This variant is present in population databases (rs374599097, gnomAD 0.1%). 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: 659490). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV002534901 SCV003750602 uncertain significance Inborn genetic diseases 2022-07-29 criteria provided, single submitter clinical testing The c.1660G>A (p.E554K) alteration is located in exon 18 (coding exon 18) of the SPINK5 gene. This alteration results from a G to A substitution at nucleotide position 1660, causing the glutamic acid (E) at amino acid position 554 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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