rs61756423

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002711.4(PPP1R3A):c.1915G>T(p.Gly639Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00611 in 1,613,586 control chromosomes in the GnomAD database, including 59 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0046 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0063 ( 53 hom. )

Consequence

PPP1R3A
NM_002711.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 3.29

Publications

13 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049847662).

BP6

Variant 7-113879177-C-A is Benign according to our data. Variant chr7-113879177-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 393403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-113879177-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 393403.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 Unknown gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3A	NM_002711.4 link	c.1915G>T	p.Gly639Cys	missense_variant	Exon 4 of 4	ENST00000284601.4	NP_002702.2	Q16821-1
PPP1R3A	XM_005250473.4 link	c.1312G>T	p.Gly438Cys	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.1915G>T	p.Gly639Cys	missense_variant	Exon 4 of 4	1	NM_002711.4	ENSP00000284601.3		Q16821-1

Frequencies

GnomAD3 genomes

AF:

0.00465

AC:

707

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000415

Gnomad FIN

AF:

0.0108

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00733

Gnomad OTH

AF:

0.00192

GnomAD2 exomes

AF:

0.00484

AC:

1214

AN:

250568

AF XY:

0.00473

show subpopulations

Gnomad AFR exome

AF:

0.00130

Gnomad AMR exome

AF:

0.00218

Gnomad ASJ exome

AF:

0.00655

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0118

Gnomad NFE exome

AF:

0.00647

Gnomad OTH exome

AF:

0.00557

GnomAD4 exome

AF:

0.00627

AC:

9157

AN:

1461474

Hom.:

Cov.:

AF XY:

0.00601

AC XY:

4373

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

33452

American (AMR)

AF:

0.00238

AC:

106

AN:

44622

Ashkenazi Jewish (ASJ)

AF:

0.00632

AC:

165

AN:

26122

East Asian (EAS)

AF:

0.00

AC:

AN:

39688

South Asian (SAS)

AF:

0.000962

AC:

AN:

86254

European-Finnish (FIN)

AF:

0.0106

AC:

566

AN:

53408

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00715

AC:

7945

AN:

1111794

Other (OTH)

AF:

0.00416

AC:

251

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

587

1174

1761

2348

2935

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

306

612

918

1224

1530

<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:

0.00465

AC:

707

AN:

152112

Hom.:

Cov.:

AF XY:

0.00468

AC XY:

348

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00106

AC:

AN:

41532

American (AMR)

AF:

0.00151

AC:

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.000415

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0108

AC:

115

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00733

AC:

498

AN:

67972

Other (OTH)

AF:

0.00190

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

114

152

190

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00612

Hom.:

Bravo

AF:

0.00377

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00733

AC:

ExAC

AF:

0.00479

AC:

581

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00507

EpiControl

AF:

0.00593

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Jun 07, 2017

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

PPP1R3A: BP4, BS2 -

Monogenic diabetes

Benign:1

Dec 07, 2018

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

ACMG criteria: BP4 (REVEL 0.122 + BP4/6 predictors, not using PP3/2 predictors), BS2 (65 cases and 59 controls in T2DM), BS1 (overall MAF in gnomAD is 0.5%): benign -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.097

Eigen

Benign

-0.033

Eigen_PC

Benign

-0.13

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0050

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

PhyloP100

3.3

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.0

REVEL

Benign

0.12

Sift

Uncertain

0.0090

Sift4G

Benign

0.074

Polyphen

0.98

Vest4

0.15

MVP

0.53

MPC

0.14

ClinPred

0.026

GERP RS

5.1

Varity_R

0.14

gMVP

0.16

Mutation Taster

=100/0

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

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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