rs2850971

chr4-101263469-C-T

Variant summary

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

The NM_000944.5(PPP3CA):c.59-67353G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 152,008 control chromosomes in the GnomAD database, including 10,258 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 0.35 (10258 hom., cov: 32)
• Consequence: PPP3CA NM_000944.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.23

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.653 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3CA	NM_000944.5	c.59-67353G>A		intron_variant		ENST00000394854.8
PPP3CA	NM_001130691.2	c.59-67353G>A		intron_variant
PPP3CA	NM_001130692.2	c.59-67353G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CA	ENST00000394854.8	c.59-67353G>A		intron_variant		1	NM_000944.5	P3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52673 AN: 151890 Hom.: 10227 Cov.: 32

Gnomad AFR AF: 0.444

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.401

Gnomad EAS AF: 0.673

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.221

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.251

Gnomad OTH AF: 0.349

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.347 AC: 52757 AN: 152008 Hom.: 10258 Cov.: 32 AF XY: 0.352 AC XY: 26186 AN XY: 74288

Gnomad4 AFR AF: 0.444

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.401

Gnomad4 EAS AF: 0.672

Gnomad4 SAS AF: 0.449

Gnomad4 FIN AF: 0.221

Gnomad4 NFE AF: 0.251

Gnomad4 OTH AF: 0.355

Alfa AF: 0.294 Hom.: 3493

Bravo AF: 0.373

Asia WGS AF: 0.555 AC: 1927 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.010
Dann	Benign	0.18

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: rs2850971; hg19: chr4-102184626;