Variant 4-101025820-CAAAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAAAAAAAA details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_000944.5(PPP3CA):c.*44dupT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.037 ( 148 hom., cov: 0)

Exomes 𝑓: 0.018 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

PPP3CA
NM_000944.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0900

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population eas. gnomad4_exome allele frequency = 0.018 (8002/443448) while in subpopulation EAS AF= 0.0306 (461/15068). AF 95% confidence interval is 0.0283. There are 1 homozygotes in gnomad4_exome. There are 4189 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 8002 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PPP3CA	NM_000944.5 link	c.*44dupT	3_prime_UTR_variant	Exon 14 of 14	ENST00000394854.8	NP_000935.1	Q08209-1A0A0S2Z4C6
PPP3CA	NM_001130691.2 link	c.*44dupT	3_prime_UTR_variant	Exon 13 of 13		NP_001124163.1	Q08209-2A0A0S2Z4B5
PPP3CA	NM_001130692.2 link	c.*44dupT	3_prime_UTR_variant	Exon 12 of 12		NP_001124164.1	Q08209-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CA	ENST00000394854 link	c.*44dupT		3_prime_UTR_variant	Exon 14 of 14	1	NM_000944.5	ENSP00000378323.3		Q08209-1

Frequencies

GnomAD3 genomes

AF:

0.0369

AC:

1277

AN:

34584

Hom.:

148

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.0178

Gnomad AMR

AF:

0.0423

Gnomad ASJ

AF:

0.0875

Gnomad EAS

AF:

0.0227

Gnomad SAS

AF:

0.0448

Gnomad FIN

AF:

0.00291

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.0428

Gnomad OTH

AF:

0.0427

GnomAD3 exomes

AF:

0.00562

AC:

239

AN:

42522

Hom.:

AF XY:

0.00603

AC XY:

136

AN XY:

22536

show subpopulations

Gnomad AFR exome

AF:

0.00603

Gnomad AMR exome

AF:

0.0177

Gnomad ASJ exome

AF:

0.00612

Gnomad EAS exome

AF:

0.0101

Gnomad SAS exome

AF:

0.0112

Gnomad FIN exome

AF:

0.000671

Gnomad NFE exome

AF:

0.00257

Gnomad OTH exome

AF:

0.00906

GnomAD4 exome

AF:

0.0180

AC:

8002

AN:

443448

Hom.:

Cov.:

AF XY:

0.0182

AC XY:

4189

AN XY:

229640

show subpopulations

Gnomad4 AFR exome

AF:

0.0142

Gnomad4 AMR exome

AF:

0.0143

Gnomad4 ASJ exome

AF:

0.0193

Gnomad4 EAS exome

AF:

0.0306

Gnomad4 SAS exome

AF:

0.0204

Gnomad4 FIN exome

AF:

0.0138

Gnomad4 NFE exome

AF:

0.0178

Gnomad4 OTH exome

AF:

0.0187

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0369

AC:

1277

AN:

34620

Hom.:

148

Cov.:

AF XY:

0.0363

AC XY:

553

AN XY:

15234

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.0422

Gnomad4 ASJ

AF:

0.0875

Gnomad4 EAS

AF:

0.0225

Gnomad4 SAS

AF:

0.0446

Gnomad4 FIN

AF:

0.00291

Gnomad4 NFE

AF:

0.0428

Gnomad4 OTH

AF:

0.0425

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over