Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001164161.2(PPP6R3):c.191A>C(p.Glu64Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).
PPP6R3 (HGNC:1173): (protein phosphatase 6 regulatory subunit 3) Protein phosphatase regulatory subunits, such as SAPS3, modulate the activity of protein phosphatase catalytic subunits by restricting substrate specificity, recruiting substrates, and determining the intracellular localization of the holoenzyme. SAPS3 is a regulatory subunit for the protein phosphatase-6 catalytic subunit (PPP6C; MIM 612725) (Stefansson and Brautigan, 2006 [PubMed 16769727]).[supplied by OMIM, Nov 2010]
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The c.191A>C (p.E64A) alteration is located in exon 3 (coding exon 1) of the PPP6R3 gene. This alteration results from a A to C substitution at nucleotide position 191, causing the glutamic acid (E) at amino acid position 64 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Loss of disorder (P = 0.0541);Loss of disorder (P = 0.0541);Loss of disorder (P = 0.0541);Loss of disorder (P = 0.0541);Loss of disorder (P = 0.0541);Loss of disorder (P = 0.0541);Loss of disorder (P = 0.0541);Loss of disorder (P = 0.0541);Loss of disorder (P = 0.0541);Loss of disorder (P = 0.0541);