Variant 10-73439887-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_021132.4(PPP3CB):c.1381A>G(p.Ile461Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000753 in 1,461,438 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

PPP3CB
NM_021132.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12555793).

BS2

High AC in GnomAdExome4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CB	NM_021132.4 linkuse as main transcript	c.1381A>G	p.Ile461Val	missense_variant	13/14	ENST00000360663.10	NP_066955.1	P16298-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPP3CB	ENST00000360663.10 linkuse as main transcript	c.1381A>G	p.Ile461Val	missense_variant	13/14	1	NM_021132.4	ENSP00000353881.5	P16298-1
PPP3CB	ENST00000394829.6 linkuse as main transcript	c.1384A>G	p.Ile462Val	missense_variant	13/14	1		ENSP00000378306.2	P16298-4
PPP3CB	ENST00000394828.6 linkuse as main transcript	c.1370-1467A>G		intron_variant		1		ENSP00000378305.2	P16298-3
PPP3CB	ENST00000430762.6 linkuse as main transcript	c.370A>G	p.Ile124Val	missense_variant	6/7	3		ENSP00000398022.2	Q5F2G0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251428

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135888

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.000163

GnomAD4 exome

AF:

0.00000753

AC:

AN:

1461438

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727032

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00000990

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

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

Dec 07, 2021

The c.1384A>G (p.I462V) alteration is located in exon 13 (coding exon 13) of the PPP3CB gene. This alteration results from a A to G substitution at nucleotide position 1384, causing the isoleucine (I) at amino acid position 462 to be replaced by a valine (V). 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

0.064

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

DANN

Benign

0.91

DEOGEN2

Benign

0.095

T;.;T

Eigen

Benign

-0.29

Eigen_PC

Benign

0.00053

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.77

T;T;T

M_CAP

Benign

0.0072

MetaRNN

Benign

0.13

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.44

N;.;.

PrimateAI

Uncertain

0.59

PROVEAN

Benign

0.090

N;N;.

REVEL

Benign

0.13

Sift

Benign

0.71

T;T;.

Sift4G

Benign

0.56

T;T;T

Polyphen

0.0

B;.;.

Vest4

0.19

MutPred

0.23

Gain of disorder (P = 0.1088);.;.;

MVP

0.35

MPC

0.53

ClinPred

0.81

GERP RS

6.2

Varity_R

0.065

gMVP

0.75

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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