Genetic Variant PPP3CC:c.1223+81T>G (chr8-22532387-T-G) – 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.1223+81T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,210,768 control chromosomes in the GnomAD database, including 151,149 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 0.56 ( 25294 hom., cov: 33)

Exomes 𝑓: 0.48 ( 125855 hom. )

Consequence

PPP3CC
NM_005605.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.300

Publications

12 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:

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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=-0.89).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CC	NM_005605.5 link	c.1223+81T>G		intron_variant	Intron 11 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.1223+81T>G		intron_variant	Intron 11 of 13	1	NM_005605.5	ENSP00000240139.5		P48454-1

Frequencies

GnomAD3 genomes

AF:

0.559

AC:

84972

AN:

151976

Hom.:

25244

Cov.:

show subpopulations

Gnomad AFR

AF:

0.770

Gnomad AMI

AF:

0.538

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.703

Gnomad SAS

AF:

0.533

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.506

Gnomad NFE

AF:

0.454

Gnomad OTH

AF:

0.507

GnomAD4 exome

AF:

0.481

AC:

509471

AN:

1058674

Hom.:

125855

AF XY:

0.481

AC XY:

260404

AN XY:

541170

show subpopulations

African (AFR)

AF:

0.779

AC:

19294

AN:

24752

American (AMR)

AF:

0.544

AC:

20219

AN:

37182

Ashkenazi Jewish (ASJ)

AF:

0.513

AC:

11484

AN:

22392

East Asian (EAS)

AF:

0.686

AC:

25682

AN:

37456

South Asian (SAS)

AF:

0.517

AC:

37656

AN:

72840

European-Finnish (FIN)

AF:

0.438

AC:

21695

AN:

49570

Middle Eastern (MID)

AF:

0.560

AC:

2736

AN:

4886

European-Non Finnish (NFE)

AF:

0.456

AC:

347470

AN:

762640

Other (OTH)

AF:

0.495

AC:

23235

AN:

46956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

12591

25182

37774

50365

62956

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9058

18116

27174

36232

45290

<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:

0.559

AC:

85079

AN:

152094

Hom.:

25294

Cov.:

AF XY:

0.559

AC XY:

41533

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.770

AC:

31948

AN:

41486

American (AMR)

AF:

0.525

AC:

8019

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1770

AN:

3462

East Asian (EAS)

AF:

0.703

AC:

3632

AN:

5166

South Asian (SAS)

AF:

0.532

AC:

2566

AN:

4826

European-Finnish (FIN)

AF:

0.435

AC:

4593

AN:

10570

Middle Eastern (MID)

AF:

0.524

AC:

153

AN:

292

European-Non Finnish (NFE)

AF:

0.453

AC:

30828

AN:

67984

Other (OTH)

AF:

0.511

AC:

1080

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1814

3627

5441

7254

9068

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

708

1416

2124

2832

3540

<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:

0.521

Hom.:

3692

Bravo

AF:

0.575

Asia WGS

AF:

0.599

AC:

2080

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.8

(source)

DANN

Benign

0.50

PhyloP100

-0.30

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