Variant 10-73479342-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 8P and 4B. PVS1BS2

The NM_001289969.2(PPP3CB):c.3G>A(p.Met1?) variant causes a start lost change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000171 in 1,461,804 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: not found (cov: 32)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

PPP3CB
NM_001289969.2 start_lost

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.29

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PVS1

Start lost variant, no new inframe start found.

BS2

High AC in GnomAdExome4 at 25 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CB	NM_021132.4 linkuse as main transcript	c.261G>A	p.Met87Ile	missense_variant	2/14	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.261G>A	p.Met87Ile	missense_variant	2/14	1	NM_021132.4	ENSP00000353881.5	P16298-1
PPP3CB	ENST00000394829.6 linkuse as main transcript	c.261G>A	p.Met87Ile	missense_variant	2/14	1		ENSP00000378306.2	P16298-4
PPP3CB	ENST00000394828.6 linkuse as main transcript	c.261G>A	p.Met87Ile	missense_variant	2/13	1		ENSP00000378305.2	P16298-3
PPP3CB	ENST00000342558.3 linkuse as main transcript	c.261G>A	p.Met87Ile	missense_variant	2/12	5		ENSP00000343147.3	Q5F2F8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000358

AC:

AN:

251358

Hom.:

AF XY:

0.0000515

AC XY:

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000171

AC:

AN:

1461804

Hom.:

Cov.:

AF XY:

0.0000275

AC XY:

AN XY:

727200

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000243

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.0000412

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jun 11, 2021

The c.261G>A (p.M87I) alteration is located in exon 2 (coding exon 2) of the PPP3CB gene. This alteration results from a G to A substitution at nucleotide position 261, causing the methionine (M) at amino acid position 87 to be replaced by an isoleucine (I). 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

Pathogenic

0.64

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.25

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

T;.;.;.

Eigen

Uncertain

0.23

Eigen_PC

Uncertain

0.35

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.95

D;D;D;D

M_CAP

Benign

0.047

MetaRNN

Benign

0.21

T;T;T;T

MetaSVM

Benign

-0.49

MutationAssessor

Benign

1.4

L;L;L;.

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-2.7

D;D;D;D

REVEL

Benign

0.24

Sift

Uncertain

0.0090

D;D;D;D

Sift4G

Benign

0.12

T;T;T;T

Polyphen

0.0020

B;B;.;.

Vest4

0.38

MutPred

0.46

Gain of methylation at K85 (P = 0.0687);Gain of methylation at K85 (P = 0.0687);Gain of methylation at K85 (P = 0.0687);Gain of methylation at K85 (P = 0.0687);

MVP

0.47

MPC

0.67

ClinPred

0.13

GERP RS

5.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.59

gMVP

0.89

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