dbSNP rs1973505: PPP1CC:p.Cys273Cys (chr12-110722198-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_002710.4(PPP1CC):c.819C>T(p.Cys273Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.151 in 1,613,756 control chromosomes in the GnomAD database, including 23,905 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 0.23 ( 6022 hom., cov: 32)

Exomes 𝑓: 0.14 ( 17883 hom. )

Consequence

PPP1CC
NM_002710.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.99

Publications

20 publications found

Variant links:

Genes affected

PPP1CC (HGNC:9283): (protein phosphatase 1 catalytic subunit gamma) The protein encoded by this gene belongs to the protein phosphatase family, PP1 subfamily. PP1 is an ubiquitous serine/threonine phosphatase that regulates many cellular processes, including cell division. It is expressed in mammalian cells as three closely related isoforms, alpha, beta/delta and gamma, which have distinct localization patterns. This gene encodes the gamma isozyme. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

PPP1CC links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP7

Synonymous conserved (PhyloP=2.99 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP1CC	NM_002710.4 link	c.819C>T	p.Cys273Cys	synonymous_variant	Exon 6 of 7	ENST00000335007.10	NP_002701.1	P36873-1A0A024RBP2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP1CC	ENST00000335007.10 link	c.819C>T	p.Cys273Cys	synonymous_variant	Exon 6 of 7	1	NM_002710.4	ENSP00000335084.5	P36873-1
PPP1CC	ENST00000550261.5 link	n.*238C>T		non_coding_transcript_exon_variant	Exon 3 of 5	5		ENSP00000447528.2	F8W0V8
PPP1CC	ENST00000550261.5 link	n.*238C>T		3_prime_UTR_variant	Exon 3 of 5	5		ENSP00000447528.2	F8W0V8

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35142

AN:

151950

Hom.:

6005

Cov.:

show subpopulations

Gnomad AFR

AF:

0.492

Gnomad AMI

AF:

0.141

Gnomad AMR

AF:

0.133

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.0730

Gnomad SAS

AF:

0.168

Gnomad FIN

AF:

0.110

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.135

Gnomad OTH

AF:

0.208

GnomAD2 exomes

AF:

0.149

AC:

37559

AN:

251334

AF XY:

0.147

show subpopulations

Gnomad AFR exome

AF:

0.498

Gnomad AMR exome

AF:

0.0915

Gnomad ASJ exome

AF:

0.176

Gnomad EAS exome

AF:

0.0681

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.131

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.142

AC:

208265

AN:

1461688

Hom.:

17883

Cov.:

AF XY:

0.142

AC XY:

103420

AN XY:

727136

show subpopulations

African (AFR)

AF:

0.511

AC:

17092

AN:

33470

American (AMR)

AF:

0.0961

AC:

4299

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

4483

AN:

26132

East Asian (EAS)

AF:

0.0614

AC:

2436

AN:

39694

South Asian (SAS)

AF:

0.164

AC:

14158

AN:

86224

European-Finnish (FIN)

AF:

0.105

AC:

5617

AN:

53414

Middle Eastern (MID)

AF:

0.204

AC:

1176

AN:

5768

European-Non Finnish (NFE)

AF:

0.134

AC:

149294

AN:

1111888

Other (OTH)

AF:

0.161

AC:

9710

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

9525

19050

28574

38099

47624

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5556

11112

16668

22224

27780

<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:

0.231

AC:

35197

AN:

152068

Hom.:

6022

Cov.:

AF XY:

0.226

AC XY:

16816

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.493

AC:

20409

AN:

41436

American (AMR)

AF:

0.132

AC:

2025

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

602

AN:

3470

East Asian (EAS)

AF:

0.0732

AC:

379

AN:

5180

South Asian (SAS)

AF:

0.168

AC:

812

AN:

4830

European-Finnish (FIN)

AF:

0.110

AC:

1164

AN:

10566

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.135

AC:

9173

AN:

67984

Other (OTH)

AF:

0.207

AC:

437

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1202

2404

3607

4809

6011

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

336

672

1008

1344

1680

<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:

0.174

Hom.:

2936

Bravo

AF:

0.246

Asia WGS

AF:

0.150

AC:

524

AN:

3478

EpiCase

AF:

0.142

EpiControl

AF:

0.147

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.63

PhyloP100

3.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=87/13

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