MKRN3 Missense Variant Annotations for Central Precocious Puberty

246.6 KB of supplementary material assesses ACMG criteria for classifying MKRN3 missense variants linked to central precocious puberty. The study, authored by figshare admin karger and published in April 2026, compares variants from clinical cohorts, HGMD, and gnomAD databases. It evaluates the performance of in silico analysis tools and proposes revised classification criteria.

Use Cases

• Benchmark in silico tool performance using sensitivity and specificity metrics from the analysis of pathogenic and benign variant sets.
• Apply revised ACMG criteria incorporating amino-acid conservation within the MKRN protein family to reclassify variants of uncertain significance.
• Study population constraint data as an additional feature for annotating the damaging effect of MKRN3 missense variants.
• Analyze familial segregation patterns over three generations as a key criterion for pathogenicity assessment in imprinted genes.

Strengths

• Data includes variants from multiple sources: a clinical CPP cohort, the HGMD database (pathogenic set), and gnomAD (benign set).
• Analysis evaluates specific metrics like sensitivity, specificity, and predictive values for variant annotation tools.
• Proposes concrete, revised ACMG criteria incorporating protein-family conservation and population constraint.

Limitations

• Dataset is very small at 246.6 KB, containing supplementary material rather than a primary data table.
• No columnar data or sample rows are provided, limiting direct computational analysis.
• Focus is exclusively on the MKRN3 gene and central precocious puberty, limiting generalizability.

Provenance

Source

figshare, uploaded by figshare admin karger, associated with a published study.

Collection Method

Variants were annotated using diverse in silico analysis tools; performance was assessed statistically.

Freshness

Last updated April 2026.