chr10-91630252-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005398.7(PPP1R3C):​c.629G>T​(p.Gly210Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00033 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00034 ( 0 hom. )

Consequence

PPP1R3C
NM_005398.7 missense

Scores

8
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34
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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15579039).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
PPP1R3CNM_005398.7 linkuse as main transcriptc.629G>T p.Gly210Val missense_variant 2/2 ENST00000238994.6 NP_005389.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
PPP1R3CENST00000238994.6 linkuse as main transcriptc.629G>T p.Gly210Val missense_variant 2/21 NM_005398.7 ENSP00000238994 P1

Frequencies

GnomAD3 genomes
AF:
0.000243
AC:
37
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000426
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.000251
AC:
63
AN:
251386
Hom.:
0
AF XY:
0.000287
AC XY:
39
AN XY:
135854
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.0000992
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.000431
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.000339
AC:
496
AN:
1461858
Hom.:
0
Cov.:
31
AF XY:
0.000347
AC XY:
252
AN XY:
727236
show subpopulations
Gnomad4 AFR exome
AF:
0.0000896
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.0000765
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.000150
Gnomad4 NFE exome
AF:
0.000416
Gnomad4 OTH exome
AF:
0.000215
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.000188
AC XY:
14
AN XY:
74316
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000426
Gnomad4 OTH
AF:
0.000478
Alfa
AF:
0.000465
Hom.:
0
Bravo
AF:
0.000272
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000465
AC:
4
ExAC
AF:
0.000247
AC:
30
EpiCase
AF:
0.000981
EpiControl
AF:
0.000533

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 GeneticsApr 27, 2024The c.629G>T (p.G210V) alteration is located in exon 1 (coding exon 1) of the PPP1R3C gene. This alteration results from a G to T substitution at nucleotide position 629, causing the glycine (G) at amino acid position 210 to be replaced by a valine (V). 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
Benign
0.15
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.38
T
Eigen
Uncertain
0.21
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Uncertain
0.85
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.031
D
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.31
T
PROVEAN
Uncertain
-4.0
D
REVEL
Benign
0.19
Sift
Uncertain
0.013
D
Sift4G
Uncertain
0.036
D
Polyphen
0.29
B
Vest4
0.21
MVP
0.83
MPC
0.23
ClinPred
0.062
T
GERP RS
4.8
Varity_R
0.39
gMVP
0.36

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: rs142799521; hg19: chr10-93390009; API