Variant chr4-101032165-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000944.5(PPP3CA):c.1339+102G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.734 in 887,348 control chromosomes in the GnomAD database, including 246,529 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.75 ( 44786 hom., cov: 32)

Exomes 𝑓: 0.73 ( 201743 hom. )

Consequence

PPP3CA
NM_000944.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.335

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.65).

BP6

Variant 4-101032165-C-T is Benign according to our data. Variant chr4-101032165-C-T is described in ClinVar as [Benign]. Clinvar id is 1243916.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
PPP3CA	NM_000944.5 linkuse as main transcript	c.1339+102G>A	intron_variant	ENST00000394854.8	NP_000935.1	Q08209-1A0A0S2Z4C6
PPP3CA	NM_001130691.2 linkuse as main transcript	c.1339+102G>A	intron_variant		NP_001124163.1	Q08209-2A0A0S2Z4B5
PPP3CA	NM_001130692.2 linkuse as main transcript	c.1213+102G>A	intron_variant		NP_001124164.1	Q08209-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CA	ENST00000394854.8 linkuse as main transcript	c.1339+102G>A		intron_variant		1	NM_000944.5	ENSP00000378323.3		Q08209-1

Frequencies

GnomAD3 genomes

AF:

0.753

AC:

114449

AN:

152034

Hom.:

44739

Cov.:

show subpopulations

Gnomad AFR

AF:

0.879

Gnomad AMI

AF:

0.904

Gnomad AMR

AF:

0.583

Gnomad ASJ

AF:

0.730

Gnomad EAS

AF:

0.147

Gnomad SAS

AF:

0.703

Gnomad FIN

AF:

0.765

Gnomad MID

AF:

0.785

Gnomad NFE

AF:

0.761

Gnomad OTH

AF:

0.744

GnomAD4 exome

AF:

0.730

AC:

536831

AN:

735196

Hom.:

201743

AF XY:

0.730

AC XY:

264853

AN XY:

362824

show subpopulations

Gnomad4 AFR exome

AF:

0.886

Gnomad4 AMR exome

AF:

0.506

Gnomad4 ASJ exome

AF:

0.723

Gnomad4 EAS exome

AF:

0.160

Gnomad4 SAS exome

AF:

0.710

Gnomad4 FIN exome

AF:

0.761

Gnomad4 NFE exome

AF:

0.757

Gnomad4 OTH exome

AF:

0.714

GnomAD4 genome

AF:

0.753

AC:

114540

AN:

152152

Hom.:

44786

Cov.:

AF XY:

0.744

AC XY:

55375

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.879

Gnomad4 AMR

AF:

0.582

Gnomad4 ASJ

AF:

0.730

Gnomad4 EAS

AF:

0.146

Gnomad4 SAS

AF:

0.701

Gnomad4 FIN

AF:

0.765

Gnomad4 NFE

AF:

0.761

Gnomad4 OTH

AF:

0.743

Alfa

AF:

0.734

Hom.:

78306

Bravo

AF:

0.739

Asia WGS

AF:

0.481

AC:

1676

AN:

3478

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 14, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.1

DANN

Benign

0.85

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