Variant 8-22475031-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005605.5(PPP3CC):c.127A>C(p.Lys43Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000226 in 1,613,190 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 1 hom. )

Consequence

PPP3CC
NM_005605.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 6.00

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008904636).

BP6

Variant 8-22475031-A-C is Benign according to our data. Variant chr8-22475031-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 737660.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd at 166 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3CC	NM_005605.5 linkuse as main transcript	c.127A>C	p.Lys43Gln	missense_variant	2/14	ENST00000240139.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CC	ENST00000240139.10 linkuse as main transcript	c.127A>C	p.Lys43Gln	missense_variant	2/14	1	NM_005605.5	P3	P48454-1

Frequencies

GnomAD3 genomes

AF:

0.00109

AC:

166

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00384

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000390

AC:

AN:

251334

Hom.:

AF XY:

0.000294

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00524

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000136

AC:

199

AN:

1460902

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

726806

show subpopulations

Gnomad4 AFR exome

AF:

0.00460

Gnomad4 AMR exome

AF:

0.000403

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000810

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.00109

AC:

166

AN:

152288

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00383

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000271

Hom.:

Bravo

AF:

0.00141

ESP6500AA

AF:

0.00499

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000420

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Apr 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.26

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.19

Cadd

Uncertain

Dann

Uncertain

0.98

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.88

LIST_S2

Pathogenic

0.98

D;D;D;D;D

M_CAP

Benign

0.018

MetaRNN

Benign

0.0089

T;T;T;T;T

MetaSVM

Benign

-0.59

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Benign

0.43

PROVEAN

Uncertain

-2.9

D;D;D;D;D

REVEL

Benign

0.24

Sift

Benign

0.054

T;T;T;T;T

Sift4G

Benign

0.11

T;T;T;T;T

Polyphen

0.25

B;B;B;.;.

Vest4

0.54

MVP

0.80

MPC

0.39

ClinPred

0.088

GERP RS

5.8

Varity_R

0.29

gMVP

0.74

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over