Genetic Variant PPP1R3C:p.Ser163Ser (chr10-91630392-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_005398.7(PPP1R3C):c.489G>A(p.Ser163Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0513 in 1,614,164 control chromosomes in the GnomAD database, including 2,528 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.035 ( 141 hom., cov: 32)

Exomes 𝑓: 0.053 ( 2387 hom. )

Consequence

PPP1R3C
NM_005398.7 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.253

Publications

7 publications found

Variant links:

Genes affected

PPP1R3C (HGNC:9293): (protein phosphatase 1 regulatory subunit 3C) This gene encodes a carbohydrate binding protein that is a subunit of the protein phosphatase 1 (PP1) complex. PP1 catalyzes reversible protein phosphorylation, which is important in a wide range of cellular activities. The encoded protein affects glycogen biosynthesis by activating glycogen synthase and limiting glycogen breakdown by reducing glycogen phosphorylase activity. DNA hypermethylation of this gene has been found in colorectal cancer patients. The encoded protein also interacts with the laforin protein, which is a protein tyrosine phosphatase implicated in Lafora disease. [provided by RefSeq, Sep 2016]

PPP1R3C links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP7

Synonymous conserved (PhyloP=-0.253 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1R3C	NM_005398.7 link	c.489G>A	p.Ser163Ser	synonymous_variant	Exon 2 of 2	ENST00000238994.6	NP_005389.1	Q9UQK1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP1R3C	ENST00000238994.6 link	c.489G>A	p.Ser163Ser	synonymous_variant	Exon 2 of 2	1	NM_005398.7	ENSP00000238994.5		Q9UQK1

Frequencies

GnomAD3 genomes

AF:

0.0350

AC:

5323

AN:

152194

Hom.:

142

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0119

Gnomad AMI

AF:

0.0175

Gnomad AMR

AF:

0.0280

Gnomad ASJ

AF:

0.0666

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0126

Gnomad FIN

AF:

0.0113

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0569

Gnomad OTH

AF:

0.0382

GnomAD2 exomes

AF:

0.0363

AC:

9119

AN:

251440

AF XY:

0.0366

show subpopulations

Gnomad AFR exome

AF:

0.0107

Gnomad AMR exome

AF:

0.0241

Gnomad ASJ exome

AF:

0.0615

Gnomad EAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.0557

Gnomad OTH exome

AF:

0.0474

GnomAD4 exome

AF:

0.0530

AC:

77410

AN:

1461852

Hom.:

2387

Cov.:

AF XY:

0.0520

AC XY:

37783

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.00905

AC:

303

AN:

33480

American (AMR)

AF:

0.0254

AC:

1134

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0602

AC:

1573

AN:

26136

East Asian (EAS)

AF:

0.000101

AC:

AN:

39700

South Asian (SAS)

AF:

0.0170

AC:

1465

AN:

86258

European-Finnish (FIN)

AF:

0.0155

AC:

827

AN:

53392

Middle Eastern (MID)

AF:

0.0510

AC:

294

AN:

5768

European-Non Finnish (NFE)

AF:

0.0619

AC:

68831

AN:

1111998

Other (OTH)

AF:

0.0493

AC:

2979

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

4785

9569

14354

19138

23923

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2590

5180

7770

10360

12950

<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:

0.0349

AC:

5320

AN:

152312

Hom.:

141

Cov.:

AF XY:

0.0311

AC XY:

2315

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.0119

AC:

494

AN:

41570

American (AMR)

AF:

0.0279

AC:

427

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.0666

AC:

231

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.0133

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.0113

AC:

120

AN:

10624

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0569

AC:

3871

AN:

68024

Other (OTH)

AF:

0.0378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

266

532

797

1063

1329

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

198

264

330

<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:

0.0501

Hom.:

370

Bravo

AF:

0.0371

Asia WGS

AF:

0.00837

AC:

AN:

3478

EpiCase

AF:

0.0613

EpiControl

AF:

0.0578

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.75

PhyloP100

-0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Computational scores

Splicing

Publications

Other links and lift over