7-113879212-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002711.4(PPP1R3A):c.1880G>A(p.Arg627Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00595 in 1,613,512 control chromosomes in the GnomAD database, including 449 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.031 ( 241 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 208 hom. )

Consequence

PPP1R3A
NM_002711.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.484

Publications

7 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014230013).

BP6

Variant 7-113879212-C-T is Benign according to our data. Variant chr7-113879212-C-T is described in ClinVar as Benign. ClinVar VariationId is 393404.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3A	NM_002711.4 link	c.1880G>A	p.Arg627Lys	missense_variant	Exon 4 of 4	ENST00000284601.4	NP_002702.2	Q16821-1
PPP1R3A	XM_005250473.4 link	c.1277G>A	p.Arg426Lys	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.1880G>A	p.Arg627Lys	missense_variant	Exon 4 of 4	1	NM_002711.4	ENSP00000284601.3		Q16821-1

Frequencies

GnomAD3 genomes

AF:

0.0308

AC:

4686

AN:

151958

Hom.:

240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0152

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0190

Gnomad NFE

AF:

0.000809

Gnomad OTH

AF:

0.0240

GnomAD2 exomes

AF:

0.00843

AC:

2114

AN:

250648

AF XY:

0.00614

show subpopulations

Gnomad AFR exome

AF:

0.108

Gnomad AMR exome

AF:

0.00690

Gnomad ASJ exome

AF:

0.00259

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000636

Gnomad OTH exome

AF:

0.00491

GnomAD4 exome

AF:

0.00336

AC:

4904

AN:

1461436

Hom.:

208

Cov.:

AF XY:

0.00292

AC XY:

2122

AN XY:

727020

show subpopulations

African (AFR)

AF:

0.109

AC:

3640

AN:

33452

American (AMR)

AF:

0.00773

AC:

345

AN:

44630

Ashkenazi Jewish (ASJ)

AF:

0.00203

AC:

AN:

26118

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39688

South Asian (SAS)

AF:

0.000209

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000562

AC:

AN:

53408

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000306

AC:

340

AN:

1111748

Other (OTH)

AF:

0.00734

AC:

443

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

324

648

972

1296

1620

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

240

360

480

600

<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:

0.0309

AC:

4693

AN:

152076

Hom.:

241

Cov.:

AF XY:

0.0288

AC XY:

2138

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.105

AC:

4344

AN:

41508

American (AMR)

AF:

0.0152

AC:

232

AN:

15240

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.000194

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.0204

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000809

AC:

AN:

67970

Other (OTH)

AF:

0.0237

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

219

439

658

878

1097

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

156

208

260

<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:

0.0123

Hom.:

162

Bravo

AF:

0.0361

ESP6500AA

AF:

0.103

AC:

455

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.0101

AC:

1227

Asia WGS

AF:

0.00549

AC:

AN:

3478

EpiCase

AF:

0.000927

EpiControl

AF:

0.00101

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

PPP1R3A-related disorder

Benign:1

Jul 31, 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). -

Monogenic diabetes

Benign:1

Nov 08, 2018

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

ACMG criteria: BA1 (10.7% in African), BS2 (142 homo in ExAC), BP4 (REVEL score 0.015 + 9 predictors)=benign -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.84

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.15

(source)

DANN

Benign

0.54

DEOGEN2

Benign

0.059

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.41

MetaRNN

Benign

0.0014

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.74

PhyloP100

-0.48

PrimateAI

Benign

0.19

PROVEAN

Benign

-0.23

REVEL

Benign

0.015

Sift

Benign

0.32

Sift4G

Benign

0.94

Polyphen

0.0

Vest4

0.049

MPC

0.044

ClinPred

0.0070

GERP RS

-3.9

Varity_R

0.043

gMVP

0.097

Mutation Taster

=100/0

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