Variant 4-101025857-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_000944.5(PPP3CA):c.*8C>T variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.00132 in 1,109,424 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0053 ( 6 hom., cov: 29)

Exomes 𝑓: 0.00071 ( 5 hom. )

Consequence

PPP3CA
NM_000944.5 3_prime_UTR

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 4.56

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 -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 4-101025857-G-A is Benign according to our data. Variant chr4-101025857-G-A is described in ClinVar as [Benign]. Clinvar id is 3044125.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00533 (779/146150) while in subpopulation AFR AF= 0.0185 (733/39640). AF 95% confidence interval is 0.0174. There are 6 homozygotes in gnomad4. There are 365 alleles in male gnomad4 subpopulation. Median coverage is 29. This position pass quality control queck.

BS2

High AC in GnomAd4 at 779 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
PPP3CA	NM_000944.5 linkuse as main transcript	c.*8C>T	3_prime_UTR_variant	14/14	ENST00000394854.8
PPP3CA	NM_001130691.2 linkuse as main transcript	c.*8C>T	3_prime_UTR_variant	13/13
PPP3CA	NM_001130692.2 linkuse as main transcript	c.*8C>T	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.*8C>T		3_prime_UTR_variant	14/14	1	NM_000944.5	P3	Q08209-1

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

777

AN:

146082

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0185

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00179

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000225

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000165

Gnomad OTH

AF:

0.00402

GnomAD3 exomes

AF:

0.00168

AC:

313

AN:

186662

Hom.:

AF XY:

0.00112

AC XY:

115

AN XY:

102472

show subpopulations

Gnomad AFR exome

AF:

0.0200

Gnomad AMR exome

AF:

0.00106

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000185

Gnomad OTH exome

AF:

0.000246

GnomAD4 exome

AF:

0.000706

AC:

680

AN:

963274

Hom.:

Cov.:

AF XY:

0.000605

AC XY:

292

AN XY:

483036

show subpopulations

Gnomad4 AFR exome

AF:

0.0240

Gnomad4 AMR exome

AF:

0.00124

Gnomad4 ASJ exome

AF:

0.0000605

Gnomad4 EAS exome

AF:

0.0000393

Gnomad4 SAS exome

AF:

0.0000683

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000110

Gnomad4 OTH exome

AF:

0.00165

GnomAD4 genome

AF:

0.00533

AC:

779

AN:

146150

Hom.:

Cov.:

AF XY:

0.00515

AC XY:

365

AN XY:

70902

show subpopulations

Gnomad4 AFR

AF:

0.0185

Gnomad4 AMR

AF:

0.00179

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000226

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000165

Gnomad4 OTH

AF:

0.00399

Alfa

AF:

0.00326

Hom.:

Bravo

AF:

0.00648

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

PPP3CA-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 20, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

DANN

Benign

0.76

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