ClinVar Miner

Submissions for variant NM_001171.6(ABCC6):c.1703T>C (p.Phe568Ser)

gnomAD frequency: 0.00036  dbSNP: rs66864704
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001857037 SCV002194505 pathogenic not provided 2025-01-06 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 568 of the ABCC6 protein (p.Phe568Ser). This variant is present in population databases (rs66864704, gnomAD 0.07%). This missense change has been observed in individual(s) with clinical features of pseudoxanthoma elasticum (PMID: 16410789; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 433241). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ABCC6 protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein RCV000499069 SCV003807381 likely pathogenic Autosomal recessive inherited pseudoxanthoma elasticum 2023-02-12 criteria provided, single submitter clinical testing ACMG classification criteria: PM3 strong, PP3 supporting, PP4
Revvity Omics, Revvity RCV001857037 SCV003824352 uncertain significance not provided 2021-03-12 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV000499069 SCV004171974 likely pathogenic Autosomal recessive inherited pseudoxanthoma elasticum 2023-01-24 criteria provided, single submitter clinical testing The missense c.1703T>C (p.Phe568Ser) variant in ABCC6 gene has been reported previously in multiple individuals affected with pseudoxanthoma elasticum (Ringpfeil et al. 2006; Legrand et al. 2017; Verschuere et al. 2021). The p.Phe568Ser variant is reported with an allele frequency of 0.001% in the gnomAD exomes database and is novel (not in any individuals) in 1000 Genomes database. This variant has been reported to the ClinVar database as Uncertain Significance / Pathogenic. The amino acid change p.Phe568Ser in ABCC6 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Phe at position 568 is changed to a Ser changing protein sequence and it might alter its composition and physico-chemical properties. Additional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic.
PXE International RCV000499069 SCV000588972 uncertain significance Autosomal recessive inherited pseudoxanthoma elasticum 2021-02-16 no assertion criteria provided research

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