Genetic Variant PPP3CC:c.*99G>C (chr8-22540901-G-C) – 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.*99G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.489 in 1,143,060 control chromosomes in the GnomAD database, including 139,673 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 ( 24990 hom., cov: 33)

Exomes 𝑓: 0.48 ( 114683 hom. )

Consequence

PPP3CC
NM_005605.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.821

Publications

29 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=-0.51).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CC	NM_005605.5 link	c.*99G>C		3_prime_UTR_variant	Exon 14 of 14	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.*99G>C		3_prime_UTR_variant	Exon 14 of 14	1	NM_005605.5	ENSP00000240139.5		P48454-1

Frequencies

GnomAD3 genomes

AF:

0.557

AC:

84702

AN:

151992

Hom.:

24941

Cov.:

show subpopulations

Gnomad AFR

AF:

0.762

Gnomad AMI

AF:

0.540

Gnomad AMR

AF:

0.525

Gnomad ASJ

AF:

0.509

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.522

Gnomad FIN

AF:

0.445

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.459

Gnomad OTH

AF:

0.509

GnomAD4 exome

AF:

0.479

AC:

474442

AN:

990950

Hom.:

114683

Cov.:

AF XY:

0.479

AC XY:

232202

AN XY:

484992

show subpopulations

African (AFR)

AF:

0.772

AC:

16980

AN:

21982

American (AMR)

AF:

0.542

AC:

7853

AN:

14496

Ashkenazi Jewish (ASJ)

AF:

0.516

AC:

8420

AN:

16326

East Asian (EAS)

AF:

0.590

AC:

18173

AN:

30790

South Asian (SAS)

AF:

0.514

AC:

21414

AN:

41654

European-Finnish (FIN)

AF:

0.451

AC:

13145

AN:

29136

Middle Eastern (MID)

AF:

0.547

AC:

1908

AN:

3486

European-Non Finnish (NFE)

AF:

0.462

AC:

365270

AN:

790220

Other (OTH)

AF:

0.496

AC:

21279

AN:

42860

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11616

23231

34847

46462

58078

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.558

AC:

84808

AN:

152110

Hom.:

24990

Cov.:

AF XY:

0.556

AC XY:

41354

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.763

AC:

31665

AN:

41506

American (AMR)

AF:

0.524

AC:

8011

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.509

AC:

1765

AN:

3468

East Asian (EAS)

AF:

0.629

AC:

3258

AN:

5178

South Asian (SAS)

AF:

0.521

AC:

2516

AN:

4826

European-Finnish (FIN)

AF:

0.445

AC:

4700

AN:

10568

Middle Eastern (MID)

AF:

0.500

AC:

147

AN:

294

European-Non Finnish (NFE)

AF:

0.459

AC:

31175

AN:

67974

Other (OTH)

AF:

0.513

AC:

1084

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1854

3708

5561

7415

9269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.349

Hom.:

921

Bravo

AF:

0.572

Asia WGS

AF:

0.570

AC:

1980

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

9.7

(source)

DANN

Benign

0.77

PhyloP100

0.82

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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8-22540901-G-C

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