dbSNP rs2469770: PPP3CC:c.771-148G>A (chr8-22522343-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_005605.5(PPP3CC):c.771-148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 614,018 control chromosomes in the GnomAD database, including 63,572 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 0.43 ( 14562 hom., cov: 32)

Exomes 𝑓: 0.46 ( 49010 hom. )

Consequence

PPP3CC
NM_005605.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Publications

7 publications found

Variant links:

Genes affected

PPP3CC (HGNC:9316): (protein phosphatase 3 catalytic subunit gamma) Calcineurin is a calcium-dependent, calmodulin-stimulated protein phosphatase involved in the downstream regulation of dopaminergic signal transduction. Calcineurin is composed of a regulatory subunit and a catalytic subunit. The protein encoded by this gene represents one of the regulatory subunits that has been found for calcineurin. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

PPP3CC Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

PPP3CC links:

ENSG00000251034 (HGNC:):

ENSG00000251034 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 (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CC	NM_005605.5 link	c.771-148G>A		intron_variant	Intron 6 of 13	ENST00000240139.10	NP_005596.2	P48454-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10 link	c.771-148G>A		intron_variant	Intron 6 of 13	1	NM_005605.5	ENSP00000240139.5		P48454-1

Frequencies

GnomAD3 genomes

AF:

0.435

AC:

66025

AN:

151748

Hom.:

14570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.377

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.488

Gnomad EAS

AF:

0.598

Gnomad SAS

AF:

0.489

Gnomad FIN

AF:

0.433

Gnomad MID

AF:

0.459

Gnomad NFE

AF:

0.447

Gnomad OTH

AF:

0.419

GnomAD4 exome

AF:

0.456

AC:

210905

AN:

462152

Hom.:

49010

AF XY:

0.457

AC XY:

112031

AN XY:

245072

show subpopulations

African (AFR)

AF:

0.377

AC:

4780

AN:

12688

American (AMR)

AF:

0.456

AC:

8222

AN:

18026

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

6822

AN:

13852

East Asian (EAS)

AF:

0.597

AC:

18464

AN:

30924

South Asian (SAS)

AF:

0.467

AC:

20297

AN:

43484

European-Finnish (FIN)

AF:

0.438

AC:

13761

AN:

31434

Middle Eastern (MID)

AF:

0.486

AC:

960

AN:

1974

European-Non Finnish (NFE)

AF:

0.444

AC:

125867

AN:

283396

Other (OTH)

AF:

0.445

AC:

11732

AN:

26374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

4914

9829

14743

19658

24572

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

796

1592

2388

3184

3980

<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:

0.435

AC:

66038

AN:

151866

Hom.:

14562

Cov.:

AF XY:

0.438

AC XY:

32517

AN XY:

74242

show subpopulations

African (AFR)

AF:

0.377

AC:

15598

AN:

41392

American (AMR)

AF:

0.452

AC:

6903

AN:

15256

Ashkenazi Jewish (ASJ)

AF:

0.488

AC:

1695

AN:

3470

East Asian (EAS)

AF:

0.597

AC:

3088

AN:

5172

South Asian (SAS)

AF:

0.489

AC:

2357

AN:

4820

European-Finnish (FIN)

AF:

0.433

AC:

4565

AN:

10532

Middle Eastern (MID)

AF:

0.469

AC:

138

AN:

294

European-Non Finnish (NFE)

AF:

0.447

AC:

30323

AN:

67912

Other (OTH)

AF:

0.418

AC:

881

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1887

3773

5660

7546

9433

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

622

1244

1866

2488

3110

<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:

0.433

Hom.:

2426

Bravo

AF:

0.432

Asia WGS

AF:

0.494

AC:

1712

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.26

(source)

DANN

Benign

0.54

PhyloP100

-1.3

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