Genetic Variant PPP1R3B:p.Gly48Glu (chr8-9141509-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_024607.4(PPP1R3B):c.143G>A(p.Gly48Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,614,174 control chromosomes in the GnomAD database, including 1,225 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.026 ( 139 hom., cov: 32)

Exomes 𝑓: 0.020 ( 1086 hom. )

Consequence

PPP1R3B
NM_024607.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.51

Publications

23 publications found

Variant links:

Genes affected

PPP1R3B (HGNC:14942): (protein phosphatase 1 regulatory subunit 3B) This gene encodes the catalytic subunit of the serine/theonine phosphatase, protein phosphatase-1. The encoded protein is expressed in liver and skeletal muscle tissue and may be involved in regulating glycogen synthesis in these tissues. This gene may be a involved in type 2 diabetes and maturity-onset diabetes of the young. Alternate splicing results in multiple transcript variants that encode the same protein.[provided by RefSeq, Jan 2011]

PPP1R3B links:

ENSG00000254340 (HGNC:58434):

ENSG00000254340 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014359355).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3B	NM_024607.4 link	c.143G>A	p.Gly48Glu	missense_variant	Exon 2 of 2	ENST00000310455.4	NP_078883.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R3B	ENST00000310455.4 link	c.143G>A	p.Gly48Glu	missense_variant	Exon 2 of 2	1	NM_024607.4	ENSP00000308318.3

Frequencies

GnomAD3 genomes

AF:

0.0256

AC:

3890

AN:

152168

Hom.:

139

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00548

Gnomad EAS

AF:

0.0709

Gnomad SAS

AF:

0.140

Gnomad FIN

AF:

0.0143

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.0224

GnomAD2 exomes

AF:

0.0311

AC:

7816

AN:

251446

AF XY:

0.0349

show subpopulations

Gnomad AFR exome

AF:

0.0418

Gnomad AMR exome

AF:

0.0103

Gnomad ASJ exome

AF:

0.00526

Gnomad EAS exome

AF:

0.0626

Gnomad FIN exome

AF:

0.0114

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0231

GnomAD4 exome

AF:

0.0204

AC:

29835

AN:

1461888

Hom.:

1086

Cov.:

AF XY:

0.0233

AC XY:

16940

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0434

AC:

1454

AN:

33480

American (AMR)

AF:

0.0111

AC:

497

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00425

AC:

111

AN:

26136

East Asian (EAS)

AF:

0.0741

AC:

2940

AN:

39700

South Asian (SAS)

AF:

0.127

AC:

10913

AN:

86258

European-Finnish (FIN)

AF:

0.0113

AC:

604

AN:

53420

Middle Eastern (MID)

AF:

0.0311

AC:

179

AN:

5762

European-Non Finnish (NFE)

AF:

0.0104

AC:

11554

AN:

1112012

Other (OTH)

AF:

0.0262

AC:

1583

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

1997

3993

5990

7986

9983

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.0256

AC:

3899

AN:

152286

Hom.:

139

Cov.:

AF XY:

0.0280

AC XY:

2087

AN XY:

74440

show subpopulations

African (AFR)

AF:

0.0410

AC:

1705

AN:

41552

American (AMR)

AF:

0.0137

AC:

209

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00548

AC:

AN:

3470

East Asian (EAS)

AF:

0.0711

AC:

368

AN:

5176

South Asian (SAS)

AF:

0.141

AC:

679

AN:

4816

European-Finnish (FIN)

AF:

0.0143

AC:

152

AN:

10612

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0104

AC:

709

AN:

68034

Other (OTH)

AF:

0.0232

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

184

368

553

737

921

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0160

Hom.:

178

Bravo

AF:

0.0224

TwinsUK

AF:

0.00971

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.0420

AC:

185

ESP6500EA

AF:

0.0107

AC:

ExAC

AF:

0.0334

AC:

4058

Asia WGS

AF:

0.107

AC:

370

AN:

3478

EpiCase

AF:

0.0105

EpiControl

AF:

0.0133

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.032

T;T

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.33

FATHMM_MKL

Benign

0.65

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.60

N;N

PhyloP100

1.5

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.20

N;N

REVEL

Benign

0.058

Sift

Benign

0.46

T;T

Sift4G

Benign

0.88

T;T

Polyphen

0.0030

B;B

Vest4

0.038

MPC

0.049

ClinPred

0.0096

GERP RS

5.8

Varity_R

0.11

gMVP

0.33

Mutation Taster

=78/22

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

Computational scores

Splicing

Publications

Other links and lift over