rs115322623

Variant names:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_002711.4(PPP1R3A):c.2640A>T(p.Arg880Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 1,612,648 control chromosomes in the GnomAD database, including 2 homozygotes. 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00016 ( 2 hom. )

Consequence

PPP1R3A
NM_002711.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.124

Publications

0 publications found

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]

PPP1R3A Gene-Disease associations (from GenCC):

diabetes mellitus, noninsulin-dependent
Inheritance: Unknown Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

PPP1R3A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0040979683).

BP6

Variant 7-113878452-T-A is Benign according to our data. Variant chr7-113878452-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 393401.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 2 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3A	NM_002711.4 link	c.2640A>T	p.Arg880Ser	missense_variant	Exon 4 of 4	ENST00000284601.4	NP_002702.2	Q16821-1
PPP1R3A	XM_005250473.4 link	c.2037A>T	p.Arg679Ser	missense_variant	Exon 5 of 5		XP_005250530.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R3A	ENST00000284601.4 link	c.2640A>T	p.Arg880Ser	missense_variant	Exon 4 of 4	1	NM_002711.4	ENSP00000284601.3		Q16821-1

Frequencies

GnomAD3 genomes

AF:

0.00176

AC:

268

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00633

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000197

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:

0.00

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000388

AC:

AN:

249704

AF XY:

0.000230

show subpopulations

Gnomad AFR exome

AF:

0.00536

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000887

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000164

AC:

240

AN:

1460490

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

726564

show subpopulations

African (AFR)

AF:

0.00616

AC:

206

AN:

33440

American (AMR)

AF:

0.000291

AC:

AN:

44618

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39672

South Asian (SAS)

AF:

0.00

AC:

AN:

86244

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111716

Other (OTH)

AF:

0.000298

AC:

AN:

60358

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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

AF:

0.00177

AC:

269

AN:

152158

Hom.:

Cov.:

AF XY:

0.00164

AC XY:

122

AN XY:

74410

show subpopulations

African (AFR)

AF:

0.00633

AC:

263

AN:

41538

American (AMR)

AF:

0.000197

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67960

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000738

Hom.:

Bravo

AF:

0.00204

ESP6500AA

AF:

0.00704

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000478

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Monogenic diabetes

Benign:1

Dec 07, 2018

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:research

ACMG criteria: BP4 (REVEL 0.031 + 8 predictors), BS2 (14 cases and 12 controls in type2diabetesgenetics.org)=Likely Benign -

PPP1R3A-related disorder

Benign:1

Aug 26, 2019

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.72

CADD

Benign

4.7

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.092

Eigen

Benign

-0.55

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.15

LIST_S2

Benign

0.46

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0041

MetaSVM

Benign

-0.95

MutationAssessor

Benign

1.1

PhyloP100

-0.12

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.42

REVEL

Benign

0.031

Sift

Benign

0.24

Sift4G

Benign

0.72

Polyphen

0.011

Vest4

0.072

MutPred

0.21

Gain of phosphorylation at R880 (P = 0.0526);

MVP

0.40

MPC

0.049

ClinPred

0.0052

GERP RS

3.4

Varity_R

0.11

gMVP

0.22

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over