Variant 4-101025858-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_000944.5(PPP3CA):c.*7C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0115 in 1,058,810 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0083 ( 14 hom., cov: 29)

Exomes 𝑓: 0.012 ( 107 hom. )

Consequence

PPP3CA
NM_000944.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.69

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 4-101025858-G-T is Benign according to our data. Variant chr4-101025858-G-T is described in ClinVar as [Benign]. Clinvar id is 1695101.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 1158 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
PPP3CA	NM_000944.5 linkuse as main transcript	c.*7C>A	3_prime_UTR_variant	14/14	ENST00000394854.8	NP_000935.1
PPP3CA	NM_001130691.2 linkuse as main transcript	c.*7C>A	3_prime_UTR_variant	13/13		NP_001124163.1
PPP3CA	NM_001130692.2 linkuse as main transcript	c.*7C>A	3_prime_UTR_variant	12/12		NP_001124164.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CA	ENST00000394854.8 linkuse as main transcript	c.*7C>A		3_prime_UTR_variant	14/14	1	NM_000944.5	ENSP00000378323	P3	Q08209-1

Frequencies

GnomAD3 genomes

AF:

0.00829

AC:

1158

AN:

139742

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00139

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00557

Gnomad ASJ

AF:

0.00118

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00116

Gnomad FIN

AF:

0.0478

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0100

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.0102

AC:

2017

AN:

198388

Hom.:

AF XY:

0.0100

AC XY:

1090

AN XY:

108478

show subpopulations

Gnomad AFR exome

AF:

0.00171

Gnomad AMR exome

AF:

0.00280

Gnomad ASJ exome

AF:

0.00148

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000675

Gnomad FIN exome

AF:

0.0455

Gnomad NFE exome

AF:

0.0104

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0120

AC:

11017

AN:

919020

Hom.:

107

Cov.:

AF XY:

0.0115

AC XY:

5360

AN XY:

464856

show subpopulations

Gnomad4 AFR exome

AF:

0.00168

Gnomad4 AMR exome

AF:

0.00339

Gnomad4 ASJ exome

AF:

0.00143

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000929

Gnomad4 FIN exome

AF:

0.0494

Gnomad4 NFE exome

AF:

0.0121

Gnomad4 OTH exome

AF:

0.00967

GnomAD4 genome

AF:

0.00828

AC:

1158

AN:

139790

Hom.:

Cov.:

AF XY:

0.00920

AC XY:

618

AN XY:

67168

show subpopulations

Gnomad4 AFR

AF:

0.00139

Gnomad4 AMR

AF:

0.00557

Gnomad4 ASJ

AF:

0.00118

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00116

Gnomad4 FIN

AF:

0.0478

Gnomad4 NFE

AF:

0.0100

Gnomad4 OTH

AF:

0.00617

Alfa

AF:

0.00759

Hom.:

Bravo

AF:

0.00540

Asia WGS

AF:

0.000578

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Aug 01, 2024

PPP3CA: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.77

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