Variant 4-101195926-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000944.5(PPP3CA):c.249G>A(p.Ala83=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0136 in 1,613,482 control chromosomes in the GnomAD database, including 1,755 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.062 ( 953 hom., cov: 32)

Exomes 𝑓: 0.0086 ( 802 hom. )

Consequence

PPP3CA
NM_000944.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.05

Variant links:

Genes affected

PPP3CA (HGNC:9314): (protein phosphatase 3 catalytic subunit alpha) Enables several functions, including ATPase binding activity; calmodulin binding activity; and calmodulin-dependent protein phosphatase activity. Involved in several processes, including calcineurin-NFAT signaling cascade; peptidyl-serine dephosphorylation; and response to calcium ion. Located in several cellular components, including cytosol; dendritic spine; and nucleoplasm. Part of calcineurin complex. Colocalizes with cytoplasmic side of plasma membrane. Implicated in developmental and epileptic encephalopathy 91. Biomarker of focal segmental glomerulosclerosis and schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

PPP3CA links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 4-101195926-C-T is Benign according to our data. Variant chr4-101195926-C-T is described in ClinVar as [Benign]. Clinvar id is 1290046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.202 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
PPP3CA	NM_000944.5 linkuse as main transcript	c.249G>A	p.Ala83=	synonymous_variant	2/14	ENST00000394854.8
PPP3CA	NM_001130691.2 linkuse as main transcript	c.249G>A	p.Ala83=	synonymous_variant	2/13
PPP3CA	NM_001130692.2 linkuse as main transcript	c.249G>A	p.Ala83=	synonymous_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CA	ENST00000394854.8 linkuse as main transcript	c.249G>A	p.Ala83=	synonymous_variant	2/14	1	NM_000944.5	P3	Q08209-1

Frequencies

GnomAD3 genomes

AF:

0.0619

AC:

9414

AN:

152046

Hom.:

951

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0284

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.0351

Gnomad SAS

AF:

0.0139

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00215

Gnomad OTH

AF:

0.0407

GnomAD3 exomes

AF:

0.0211

AC:

5297

AN:

250614

Hom.:

398

AF XY:

0.0169

AC XY:

2293

AN XY:

135424

show subpopulations

Gnomad AFR exome

AF:

0.211

Gnomad AMR exome

AF:

0.0142

Gnomad ASJ exome

AF:

0.00120

Gnomad EAS exome

AF:

0.0436

Gnomad SAS exome

AF:

0.00819

Gnomad FIN exome

AF:

0.0000464

Gnomad NFE exome

AF:

0.00215

Gnomad OTH exome

AF:

0.0113

GnomAD4 exome

AF:

0.00858

AC:

12545

AN:

1461318

Hom.:

802

Cov.:

AF XY:

0.00794

AC XY:

5769

AN XY:

726942

show subpopulations

Gnomad4 AFR exome

AF:

0.206

Gnomad4 AMR exome

AF:

0.0160

Gnomad4 ASJ exome

AF:

0.000997

Gnomad4 EAS exome

AF:

0.0239

Gnomad4 SAS exome

AF:

0.00809

Gnomad4 FIN exome

AF:

0.0000750

Gnomad4 NFE exome

AF:

0.00181

Gnomad4 OTH exome

AF:

0.0184

GnomAD4 genome

AF:

0.0620

AC:

9440

AN:

152164

Hom.:

953

Cov.:

AF XY:

0.0595

AC XY:

4424

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.205

Gnomad4 AMR

AF:

0.0283

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.0352

Gnomad4 SAS

AF:

0.0139

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00215

Gnomad4 OTH

AF:

0.0402

Alfa

AF:

0.0213

Hom.:

122

Bravo

AF:

0.0712

Asia WGS

AF:

0.0300

AC:

104

AN:

3478

EpiCase

AF:

0.00284

EpiControl

AF:

0.00303

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

5.7

DANN

Benign

0.60

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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