rs28664200

Positions:

• chr4-101330344-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.374

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]

MIR1255A (HGNC:):

ACMG classification

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/exons	MANE	Protein	UniProt
PPP3CA	NM_000944.5	c.58+16395A>G		intron_variant		ENST00000394854.8	NP_000935.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CA	ENST00000394854.8	c.58+16395A>G		intron_variant		1	NM_000944.5	ENSP00000378323.3

Frequencies

GnomAD3 genomes AF: 0.298 AC: 44866 AN: 150558 Hom.: 7136 Cov.: 31

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

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.: 0 AF XY: 0.337 AC XY: 64298 AN XY: 190800

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.: 31 AF XY: 0.311 AC XY: 22909 AN XY: 73634

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

Other links and lift over

dbSNP: rs28664200; hg19: chr4-102251501; COSMIC: COSV59931001;