rs193920921

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005398.7(PPP1R3C):​c.458A>G​(p.Gln153Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

PPP1R3C
NM_005398.7 missense

Scores

4
15

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 3.49

Publications

2 publications found
Variant links:
Genes affected
PPP1R3C (HGNC:9293): (protein phosphatase 1 regulatory subunit 3C) This gene encodes a carbohydrate binding protein that is a subunit of the protein phosphatase 1 (PP1) complex. PP1 catalyzes reversible protein phosphorylation, which is important in a wide range of cellular activities. The encoded protein affects glycogen biosynthesis by activating glycogen synthase and limiting glycogen breakdown by reducing glycogen phosphorylase activity. DNA hypermethylation of this gene has been found in colorectal cancer patients. The encoded protein also interacts with the laforin protein, which is a protein tyrosine phosphatase implicated in Lafora disease. [provided by RefSeq, Sep 2016]

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34115106).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP1R3CNM_005398.7 linkc.458A>G p.Gln153Arg missense_variant Exon 2 of 2 ENST00000238994.6 NP_005389.1 Q9UQK1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP1R3CENST00000238994.6 linkc.458A>G p.Gln153Arg missense_variant Exon 2 of 2 1 NM_005398.7 ENSP00000238994.5 Q9UQK1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461882
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727240
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33478
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53412
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00000180
AC:
2
AN:
1112010
Other (OTH)
AF:
0.00
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.500
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Prostate cancer Uncertain:1
-
Science for Life laboratory, Karolinska Institutet
Significance:Uncertain significance
Review Status:no assertion criteria provided
Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.49
T
Eigen
Benign
0.18
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.85
T
M_CAP
Benign
0.029
D
MetaRNN
Benign
0.34
T
MetaSVM
Benign
-0.74
T
MutationAssessor
Benign
1.4
L
PhyloP100
3.5
PrimateAI
Benign
0.43
T
PROVEAN
Benign
-2.2
N
REVEL
Benign
0.14
Sift
Benign
0.14
T
Sift4G
Benign
0.076
T
Polyphen
0.39
B
Vest4
0.37
MutPred
0.60
Gain of ubiquitination at K154 (P = 0.0671);
MVP
0.74
MPC
0.26
ClinPred
0.80
D
GERP RS
5.8
Varity_R
0.43
gMVP
0.45
Mutation Taster
=78/22
polymorphism

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

Other links and lift over

dbSNP: rs193920921; hg19: chr10-93390180; COSMIC: COSV53289092; API