Variant 4-101025820-CAAAAAAAAAAAAAAAAAA-CAAAAAAAAAAAAA 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.*40_*44delTTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 441,246 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00052 ( 0 hom., cov: 0)

Exomes 𝑓: 0.020 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PPP3CA
NM_000944.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.89

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 -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0204 (8984/441246) while in subpopulation SAS AF= 0.0247 (854/34620). AF 95% confidence interval is 0.0233. There are 0 homozygotes in gnomad4_exome. There are 4726 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 8984 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
PPP3CA	NM_000944.5 link	c.40_44delTTTTT	3_prime_UTR_variant	Exon 14 of 14	ENST00000394854.8	NP_000935.1	Q08209-1A0A0S2Z4C6
PPP3CA	NM_001130691.2 link	c.40_44delTTTTT	3_prime_UTR_variant	Exon 13 of 13		NP_001124163.1	Q08209-2A0A0S2Z4B5
PPP3CA	NM_001130692.2 link	c.40_44delTTTTT	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.40_44delTTTTT		3_prime_UTR_variant	Exon 14 of 14	1	NM_000944.5	ENSP00000378323.3		Q08209-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

34560

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00201

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000933

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0127

AC:

541

AN:

42522

Hom.:

AF XY:

0.0128

AC XY:

288

AN XY:

22536

show subpopulations

Gnomad AFR exome

AF:

0.0159

Gnomad AMR exome

AF:

0.0244

Gnomad ASJ exome

AF:

0.0138

Gnomad EAS exome

AF:

0.0229

Gnomad SAS exome

AF:

0.0191

Gnomad FIN exome

AF:

0.00101

Gnomad NFE exome

AF:

0.00954

Gnomad OTH exome

AF:

0.0109

GnomAD4 exome

AF:

0.0204

AC:

8984

AN:

441246

Hom.:

AF XY:

0.0207

AC XY:

4726

AN XY:

228432

show subpopulations

Gnomad4 AFR exome

AF:

0.0212

Gnomad4 AMR exome

AF:

0.0144

Gnomad4 ASJ exome

AF:

0.0245

Gnomad4 EAS exome

AF:

0.0173

Gnomad4 SAS exome

AF:

0.0247

Gnomad4 FIN exome

AF:

0.0178

Gnomad4 NFE exome

AF:

0.0201

Gnomad4 OTH exome

AF:

0.0249

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000520

AC:

AN:

34596

Hom.:

Cov.:

AF XY:

0.000329

AC XY:

AN XY:

15220

show subpopulations

Gnomad4 AFR

AF:

0.00201

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000933

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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