dbSNP rs28664200: PPP3CA:c.58+16395A>G (chr4-101330344-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000944.5(PPP3CA):c.58+16395A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.323 in 483,962 control chromosomes in the GnomAD database, including 27,126 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.30 ( 7149 hom., cov: 31)

Exomes 𝑓: 0.33 ( 19977 hom. )

Consequence

PPP3CA
NM_000944.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.374

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:

MIR1255A (HGNC:35320): (microRNA 1255a) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR1255A links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.487 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CA	NM_000944.5 link	c.58+16395A>G		intron_variant	Intron 1 of 13	ENST00000394854.8	NP_000935.1	Q08209-1A0A0S2Z4C6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CA	ENST00000394854.8 link	c.58+16395A>G		intron_variant	Intron 1 of 13	1	NM_000944.5	ENSP00000378323.3		Q08209-1

Frequencies

GnomAD3 genomes

AF:

0.298

AC:

44866

AN:

150558

Hom.:

7136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.401

Gnomad AMR

AF:

0.385

Gnomad ASJ

AF:

0.262

Gnomad EAS

AF:

0.504

Gnomad SAS

AF:

0.427

Gnomad FIN

AF:

0.424

Gnomad MID

AF:

0.163

Gnomad NFE

AF:

0.281

Gnomad OTH

AF:

0.286

GnomAD3 exomes

AF:

0.343

AC:

62899

AN:

183276

Hom.:

11665

AF XY:

0.340

AC XY:

33854

AN XY:

99710

show subpopulations

Gnomad AFR exome

AF:

0.220

Gnomad AMR exome

AF:

0.459

Gnomad ASJ exome

AF:

0.274

Gnomad EAS exome

AF:

0.503

Gnomad SAS exome

AF:

0.410

Gnomad FIN exome

AF:

0.410

Gnomad NFE exome

AF:

0.277

Gnomad OTH exome

AF:

0.310

GnomAD4 exome

AF:

0.335

AC:

111520

AN:

333280

Hom.:

19977

Cov.:

AF XY:

0.337

AC XY:

64298

AN XY:

190800

show subpopulations

Gnomad4 AFR exome

AF:

0.222

Gnomad4 AMR exome

AF:

0.458

Gnomad4 ASJ exome

AF:

0.272

Gnomad4 EAS exome

AF:

0.500

Gnomad4 SAS exome

AF:

0.407

Gnomad4 FIN exome

AF:

0.405

Gnomad4 NFE exome

AF:

0.282

Gnomad4 OTH exome

AF:

0.305

GnomAD4 genome

AF:

0.298

AC:

44907

AN:

150682

Hom.:

7149

Cov.:

AF XY:

0.311

AC XY:

22909

AN XY:

73634

show subpopulations

Gnomad4 AFR

AF:

0.225

Gnomad4 AMR

AF:

0.386

Gnomad4 ASJ

AF:

0.262

Gnomad4 EAS

AF:

0.503

Gnomad4 SAS

AF:

0.426

Gnomad4 FIN

AF:

0.424

Gnomad4 NFE

AF:

0.281

Gnomad4 OTH

AF:

0.293

Alfa

AF:

0.275

Hom.:

2541

Bravo

AF:

0.293

Asia WGS

AF:

0.477

AC:

1656

AN:

3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

2.1

DANN

Benign

0.57

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