8-9141164-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_024607.4(PPP1R3B):​c.488G>A​(p.Arg163Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

PPP1R3B
NM_024607.4 missense

Scores

7
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
Variant links:
Genes affected
PPP1R3B (HGNC:14942): (protein phosphatase 1 regulatory subunit 3B) This gene encodes the catalytic subunit of the serine/theonine phosphatase, protein phosphatase-1. The encoded protein is expressed in liver and skeletal muscle tissue and may be involved in regulating glycogen synthesis in these tissues. This gene may be a involved in type 2 diabetes and maturity-onset diabetes of the young. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Jan 2011]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.96

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP1R3BNM_024607.4 linkc.488G>A p.Arg163Lys missense_variant Exon 2 of 2 ENST00000310455.4 NP_078883.2 Q86XI6
PPP1R3BNM_001201329.2 linkc.488G>A p.Arg163Lys missense_variant Exon 2 of 2 NP_001188258.1 Q86XI6
PPP1R3BXM_006716253.4 linkc.488G>A p.Arg163Lys missense_variant Exon 2 of 2 XP_006716316.1 Q86XI6
PPP1R3BXM_047422235.1 linkc.488G>A p.Arg163Lys missense_variant Exon 2 of 2 XP_047278191.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP1R3BENST00000310455.4 linkc.488G>A p.Arg163Lys missense_variant Exon 2 of 2 1 NM_024607.4 ENSP00000308318.3 Q86XI6
PPP1R3BENST00000519699.1 linkc.488G>A p.Arg163Lys missense_variant Exon 2 of 2 2 ENSP00000428642.1 Q86XI6

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000159
AC:
4
AN:
251464
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135902
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1461892
Hom.:
0
Cov.:
35
AF XY:
0.00000138
AC XY:
1
AN XY:
727246
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Aug 21, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.488G>A (p.R163K) alteration is located in exon 2 (coding exon 1) of the PPP1R3B gene. This alteration results from a G to A substitution at nucleotide position 488, causing the arginine (R) at amino acid position 163 to be replaced by a lysine (K). 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
0.66
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Pathogenic
0.26
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.41
T;T
Eigen
Pathogenic
0.79
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Uncertain
0.97
D
M_CAP
Uncertain
0.087
D
MetaRNN
Pathogenic
0.96
D;D
MetaSVM
Uncertain
0.086
D
MutationAssessor
Uncertain
2.6
M;M
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.0
D;D
REVEL
Pathogenic
0.69
Sift
Uncertain
0.0050
D;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
1.0
D;D
Vest4
0.92
MutPred
0.80
Gain of ubiquitination at R163 (P = 0.0539);Gain of ubiquitination at R163 (P = 0.0539);
MVP
0.89
MPC
0.30
ClinPred
0.78
D
GERP RS
5.9
Varity_R
0.60
gMVP
0.85

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: rs1344611160; hg19: chr8-8998674; API