rs141223649

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002711.4(PPP1R3A):​c.628C>T​(p.Arg210Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000174 in 1,613,214 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00093 ( 1 hom., cov: 32)
Exomes 𝑓: 0.000096 ( 1 hom. )

Consequence

PPP1R3A
NM_002711.4 missense

Scores

4
7
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.42
Variant links:
Genes affected
PPP1R3A (HGNC:9291): (protein phosphatase 1 regulatory subunit 3A) The glycogen-associated form of protein phosphatase-1 (PP1) derived from skeletal muscle is a heterodimer composed of a 37-kD catalytic subunit and a 124-kD targeting and regulatory subunit. This gene encodes the regulatory subunit which binds to muscle glycogen with high affinity, thereby enhancing dephosphorylation of glycogen-bound substrates for PP1 such as glycogen synthase and glycogen phosphorylase kinase. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.023028404).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
PPP1R3ANM_002711.4 linkc.628C>T p.Arg210Cys missense_variant Exon 1 of 4 ENST00000284601.4 NP_002702.2 Q16821-1
PPP1R3AXM_005250473.4 linkc.97-72C>T intron_variant Intron 1 of 4 XP_005250530.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
PPP1R3AENST00000284601.4 linkc.628C>T p.Arg210Cys missense_variant Exon 1 of 4 1 NM_002711.4 ENSP00000284601.3 Q16821-1
PPP1R3AENST00000284602.1 linkn.179-72C>T intron_variant Intron 1 of 4 1 ENSP00000284602.1 Q16821-2
PPP1R3AENST00000449795.5 linkc.-181-36049C>T intron_variant Intron 1 of 3 3 ENSP00000401278.1 C9JZB3

Frequencies

GnomAD3 genomes
AF:
0.000928
AC:
141
AN:
151900
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00307
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.000479
GnomAD3 exomes
AF:
0.000323
AC:
81
AN:
250710
Hom.:
1
AF XY:
0.000244
AC XY:
33
AN XY:
135516
show subpopulations
Gnomad AFR exome
AF:
0.00413
Gnomad AMR exome
AF:
0.000261
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000164
GnomAD4 exome
AF:
0.0000958
AC:
140
AN:
1461196
Hom.:
1
Cov.:
31
AF XY:
0.0000922
AC XY:
67
AN XY:
726892
show subpopulations
Gnomad4 AFR exome
AF:
0.00239
Gnomad4 AMR exome
AF:
0.000268
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000404
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000180
Gnomad4 OTH exome
AF:
0.000149
GnomAD4 genome
AF:
0.000928
AC:
141
AN:
152018
Hom.:
1
Cov.:
32
AF XY:
0.00101
AC XY:
75
AN XY:
74314
show subpopulations
Gnomad4 AFR
AF:
0.00306
Gnomad4 AMR
AF:
0.000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.000474
Alfa
AF:
0.000144
Hom.:
0
Bravo
AF:
0.00116
ESP6500AA
AF:
0.00545
AC:
24
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.000387
AC:
47
Asia WGS
AF:
0.000578
AC:
2
AN:
3476

ClinVar

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

Submissions by phenotype

Monogenic diabetes Uncertain:1
Apr 07, 2017
Personalized Diabetes Medicine Program, University of Maryland School of Medicine
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: research

ACMG Criteria:PP3 (6 predictors), BP4 (4 predictors) -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.40
BayesDel_addAF
Benign
-0.049
T
BayesDel_noAF
Pathogenic
0.16
CADD
Pathogenic
32
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.35
T
Eigen
Uncertain
0.64
Eigen_PC
Pathogenic
0.69
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.065
D
MetaRNN
Benign
0.023
T
MetaSVM
Benign
-0.64
T
MutationAssessor
Benign
1.6
L
PrimateAI
Uncertain
0.68
T
PROVEAN
Pathogenic
-6.4
D
REVEL
Uncertain
0.45
Sift
Benign
0.10
T
Sift4G
Uncertain
0.016
D
Polyphen
1.0
D
Vest4
0.67
MVP
0.86
MPC
0.34
ClinPred
0.098
T
GERP RS
6.1
Varity_R
0.39
gMVP
0.71

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: rs141223649; hg19: chr7-113558424; COSMIC: COSV52876286; API