rs1799999

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_002711.4(PPP1R3A):c.2713G>T(p.Asp905Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 1,611,778 control chromosomes in the GnomAD database, including 29,281 homozygotes. 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 Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.17 ( 3429 hom., cov: 32)

Exomes 𝑓: 0.14 ( 25852 hom. )

Consequence

PPP1R3A
NM_002711.4 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2O:1

Conservation

PhyloP100: 3.23

Publications

62 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 -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=8.817586E-6).

BP6

Variant 7-113878379-C-A is Benign according to our data. Variant chr7-113878379-C-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 8706.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3A	NM_002711.4 link	c.2713G>T	p.Asp905Tyr	missense_variant	Exon 4 of 4	ENST00000284601.4	NP_002702.2	Q16821-1
PPP1R3A	XM_005250473.4 link	c.2110G>T	p.Asp704Tyr	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.2713G>T	p.Asp905Tyr	missense_variant	Exon 4 of 4	1	NM_002711.4	ENSP00000284601.3		Q16821-1

Frequencies

GnomAD3 genomes

AF:

0.174

AC:

26465

AN:

151784

Hom.:

3426

Cov.:

show subpopulations

Gnomad AFR

AF:

0.194

Gnomad AMI

AF:

0.122

Gnomad AMR

AF:

0.213

Gnomad ASJ

AF:

0.207

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.398

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0950

Gnomad OTH

AF:

0.179

GnomAD2 exomes

AF:

0.221

AC:

55132

AN:

249384

AF XY:

0.223

show subpopulations

Gnomad AFR exome

AF:

0.195

Gnomad AMR exome

AF:

0.259

Gnomad ASJ exome

AF:

0.213

Gnomad EAS exome

AF:

0.684

Gnomad FIN exome

AF:

0.205

Gnomad NFE exome

AF:

0.0985

Gnomad OTH exome

AF:

0.184

GnomAD4 exome

AF:

0.142

AC:

206696

AN:

1459874

Hom.:

25852

Cov.:

AF XY:

0.149

AC XY:

107979

AN XY:

726318

show subpopulations

African (AFR)

AF:

0.197

AC:

6583

AN:

33442

American (AMR)

AF:

0.257

AC:

11460

AN:

44590

Ashkenazi Jewish (ASJ)

AF:

0.216

AC:

5630

AN:

26108

East Asian (EAS)

AF:

0.688

AC:

27295

AN:

39676

South Asian (SAS)

AF:

0.389

AC:

33521

AN:

86242

European-Finnish (FIN)

AF:

0.194

AC:

10089

AN:

52076

Middle Eastern (MID)

AF:

0.165

AC:

952

AN:

5762

European-Non Finnish (NFE)

AF:

0.0908

AC:

100924

AN:

1111622

Other (OTH)

AF:

0.170

AC:

10242

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

10584

21169

31753

42338

52922

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4222

8444

12666

16888

21110

<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:

0.174

AC:

26493

AN:

151904

Hom.:

3429

Cov.:

AF XY:

0.188

AC XY:

13954

AN XY:

74244

show subpopulations

African (AFR)

AF:

0.193

AC:

8020

AN:

41472

American (AMR)

AF:

0.214

AC:

3266

AN:

15234

Ashkenazi Jewish (ASJ)

AF:

0.207

AC:

716

AN:

3466

East Asian (EAS)

AF:

0.671

AC:

3435

AN:

5122

South Asian (SAS)

AF:

0.398

AC:

1917

AN:

4812

European-Finnish (FIN)

AF:

0.204

AC:

2153

AN:

10566

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0950

AC:

6456

AN:

67928

Other (OTH)

AF:

0.180

AC:

377

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1007

2014

3021

4028

5035

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

290

580

870

1160

1450

<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:

0.136

Hom.:

8522

Bravo

AF:

0.178

TwinsUK

AF:

0.0914

AC:

339

ALSPAC

AF:

0.0867

AC:

334

ESP6500AA

AF:

0.195

AC:

858

ESP6500EA

AF:

0.105

AC:

902

ExAC

AF:

0.219

AC:

26546

Asia WGS

AF:

0.439

AC:

1524

AN:

3478

EpiCase

AF:

0.0978

EpiControl

AF:

0.0986

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2Other:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Type 2 diabetes mellitus

Uncertain:1

Jan 01, 2016

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: BP6,PP5. This variant was detected in homozygous state. -

PPP1R3A-related disorder

Benign:1

Oct 17, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

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

not provided

Benign:1

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 7581368) -

Insulin resistance, susceptibility to

Other:1

Aug 01, 1995

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.50

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.72

MetaRNN

Benign

0.0000088

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

PhyloP100

3.2

PrimateAI

Benign

0.28

PROVEAN

Uncertain

-2.4

REVEL

Benign

0.081

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.014

Polyphen

0.98

Vest4

0.15

MPC

0.31

ClinPred

0.044

GERP RS

5.6

Varity_R

0.20

gMVP

0.37

Mutation Taster

=98/2

polymorphism (auto)

(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