Variant 4-101025791-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_000944.5(PPP3CA):c.*74A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0926 in 1,221,396 control chromosomes in the GnomAD database, including 7,748 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.16 ( 2182 hom., cov: 22)

Exomes 𝑓: 0.085 ( 5566 hom. )

Consequence

PPP3CA
NM_000944.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.360

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-101025791-T-C is Benign according to our data. Variant chr4-101025791-T-C is described in ClinVar as [Benign]. Clinvar id is 1247668.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PPP3CA	NM_000944.5 linkuse as main transcript	c.*74A>G	3_prime_UTR_variant	14/14	ENST00000394854.8
PPP3CA	NM_001130691.2 linkuse as main transcript	c.*74A>G	3_prime_UTR_variant	13/13
PPP3CA	NM_001130692.2 linkuse as main transcript	c.*74A>G	3_prime_UTR_variant	12/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CA	ENST00000394854.8 linkuse as main transcript	c.*74A>G		3_prime_UTR_variant	14/14	1	NM_000944.5	P3	Q08209-1

Frequencies

GnomAD3 genomes

AF:

0.161

AC:

20291

AN:

125700

Hom.:

2182

Cov.:

show subpopulations

Gnomad AFR

AF:

0.336

Gnomad AMI

AF:

0.00339

Gnomad AMR

AF:

0.121

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.134

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.163

Gnomad MID

AF:

0.201

Gnomad NFE

AF:

0.0780

Gnomad OTH

AF:

0.146

GnomAD4 exome

AF:

0.0847

AC:

92813

AN:

1095632

Hom.:

5566

Cov.:

AF XY:

0.0873

AC XY:

47570

AN XY:

545150

show subpopulations

Gnomad4 AFR exome

AF:

0.300

Gnomad4 AMR exome

AF:

0.0539

Gnomad4 ASJ exome

AF:

0.114

Gnomad4 EAS exome

AF:

0.145

Gnomad4 SAS exome

AF:

0.189

Gnomad4 FIN exome

AF:

0.0985

Gnomad4 NFE exome

AF:

0.0678

Gnomad4 OTH exome

AF:

0.0993

GnomAD4 genome

AF:

0.162

AC:

20311

AN:

125764

Hom.:

2182

Cov.:

AF XY:

0.170

AC XY:

9914

AN XY:

58192

show subpopulations

Gnomad4 AFR

AF:

0.336

Gnomad4 AMR

AF:

0.121

Gnomad4 ASJ

AF:

0.132

Gnomad4 EAS

AF:

0.133

Gnomad4 SAS

AF:

0.216

Gnomad4 FIN

AF:

0.163

Gnomad4 NFE

AF:

0.0780

Gnomad4 OTH

AF:

0.153

Alfa

AF:

0.0910

Hom.:

920

Bravo

AF:

0.147

Asia WGS

AF:

0.213

AC:

742

AN:

3474

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

GeneDx

May 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

3.2

DANN

Benign

0.71

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