ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.10583A>G (p.Asn3528Ser)

gnomAD frequency: 0.00001  dbSNP: rs886061612
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000364249 SCV000464035 uncertain significance Autosomal recessive polycystic kidney disease 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Fulgent Genetics, Fulgent Genetics RCV002480235 SCV002782608 uncertain significance Polycystic kidney disease 4 2022-05-17 criteria provided, single submitter clinical testing
Invitae RCV000364249 SCV002957383 uncertain significance Autosomal recessive polycystic kidney disease 2021-08-31 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 3528 of the PKHD1 protein (p.Asn3528Ser). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 357412). 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 serine 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 RCV002524495 SCV003593731 uncertain significance Inborn genetic diseases 2021-10-29 criteria provided, single submitter clinical testing The c.10583A>G (p.N3528S) alteration is located in exon 61 (coding exon 60) of the PKHD1 gene. This alteration results from a A to G substitution at nucleotide position 10583, causing the asparagine (N) at amino acid position 3528 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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