Variant 10-73495874-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_021132.4(PPP3CB):c.16C>G(p.Pro6Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000135 in 147,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000014 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000091 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPP3CB
NM_021132.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39

Variant links:

Genes affected

PPP3CB (HGNC:9315): (protein phosphatase 3 catalytic subunit beta) Enables several functions, including calmodulin binding activity; calmodulin-dependent protein phosphatase activity; and protein phosphatase 2B binding activity. Involved in calcineurin-NFAT signaling cascade; positive regulation of transcription by RNA polymerase II; and protein dephosphorylation. Located in cytoplasm. Part of calcineurin complex. Implicated in aortic valve stenosis. Biomarker of focal segmental glomerulosclerosis and schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

PPP3CB links:

PPP3CB-AS1 (HGNC:50750): (PPP3CB antisense RNA 1 (head to head))

PPP3CB-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.1573126).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CB	NM_021132.4 link	c.16C>G	p.Pro6Ala	missense_variant	1/14	ENST00000360663.10	NP_066955.1	P16298-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CB	ENST00000360663.10 link	c.16C>G	p.Pro6Ala	missense_variant	1/14	1	NM_021132.4	ENSP00000353881.5		P16298-1

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

147756

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000405

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000915

AC:

AN:

1202832

Hom.:

Cov.:

AF XY:

0.0000119

AC XY:

AN XY:

589072

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000955

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000342

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000206

GnomAD4 genome

AF:

0.0000135

AC:

AN:

147756

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72104

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000405

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 10, 2024

The c.16C>G (p.P6A) alteration is located in exon 1 (coding exon 1) of the PPP3CB gene. This alteration results from a C to G substitution at nucleotide position 16, causing the proline (P) at amino acid position 6 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.45

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.11

T;.;.;.

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.027

LIST_S2

Benign

0.80

T;T;T;T

M_CAP

Pathogenic

0.70

MetaRNN

Benign

0.16

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;N;.

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

0.74

N;N;N;N

REVEL

Benign

0.055

Sift

Pathogenic

0.0

D;D;D;D

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.022

B;B;.;.

Vest4

0.23

MutPred

0.17

Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);Loss of loop (P = 0.0022);

MVP

0.16

MPC

0.58

ClinPred

0.37

GERP RS

2.9

Varity_R

0.18

gMVP

0.34

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