Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001164161.2(PPP6R3):c.1229C>T(p.Ala410Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,611,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. 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]
Uncertain significance, criteria provided, single submitter
clinical testing
Ambry Genetics
Jan 29, 2024
The c.1229C>T (p.A410V) alteration is located in exon 11 (coding exon 9) of the PPP6R3 gene. This alteration results from a C to T substitution at nucleotide position 1229, causing the alanine (A) at amino acid position 410 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Loss of disorder (P = 0.0593);.;Loss of disorder (P = 0.0593);Loss of disorder (P = 0.0593);Loss of disorder (P = 0.0593);Loss of disorder (P = 0.0593);.;.;Loss of disorder (P = 0.0593);.;