Genetic Variant PPP3CC:c.1223+81T>C (chr8-22532387-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_005605.5(PPP3CC):c.1223+81T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000942 in 1,061,204 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 9.4e-7 ( 0 hom. )

Consequence

PPP3CC
NM_005605.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.300

Publications

0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.42e-7

AC:

AN:

1061204

Hom.:

AF XY:

0.00000184

AC XY:

AN XY:

542386

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24790

American (AMR)

AF:

0.00

AC:

AN:

37276

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22430

East Asian (EAS)

AF:

0.00

AC:

AN:

37492

South Asian (SAS)

AF:

0.0000137

AC:

AN:

72992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49640

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4888

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

764658

Other (OTH)

AF:

0.00

AC:

AN:

47038

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

3.3

(source)

DANN

Benign

0.66

PhyloP100

-0.30

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over