11-68537855-A-C

Variant summary

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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Consequence

PPP6R3
NM_001164161.2 missense

Scores

8
8
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.21
Variant links:
Genes affected
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPP6R3NM_001164161.2 linkuse as main transcriptc.191A>C p.Glu64Ala missense_variant 3/24 ENST00000393800.7 NP_001157633.1 Q5H9R7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPP6R3ENST00000393800.7 linkuse as main transcriptc.191A>C p.Glu64Ala missense_variant 3/241 NM_001164161.2 ENSP00000377389.2 Q5H9R7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsNov 21, 2024The 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.77
BayesDel_addAF
Pathogenic
0.28
D
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
28
DANN
Uncertain
1.0
DEOGEN2
Benign
0.31
T;T;.;T;.;.;.;.;T;T
Eigen
Pathogenic
0.85
Eigen_PC
Pathogenic
0.80
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.90
D;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.028
D
MetaRNN
Uncertain
0.74
D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
0.00050
D
MutationAssessor
Pathogenic
3.2
M;.;M;.;M;M;M;M;.;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-4.9
D;D;D;D;D;D;D;D;D;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.0030
D;D;D;D;D;D;D;D;D;D
Sift4G
Uncertain
0.0040
D;D;D;D;D;D;D;D;D;D
Polyphen
1.0
D;.;D;.;D;D;D;D;.;.
Vest4
0.83
MutPred
0.61
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);
MVP
0.45
MPC
1.0
ClinPred
1.0
D
GERP RS
5.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.65
gMVP
0.53

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2099278498; hg19: chr11-68305323; API