rs3804423

Positions:

• chr4-101266705-G-A

Variant summary

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

The NM_000944.5(PPP3CA):​c.59-70589C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00443 in 152,214 control chromosomes in the GnomAD database, including 15 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 0.0044 (15 hom., cov: 32)
• Consequence: PPP3CA NM_000944.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.606

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3CA	NM_000944.5	c.59-70589C>T		intron_variant		ENST00000394854.8
PPP3CA	NM_001130691.2	c.59-70589C>T		intron_variant
PPP3CA	NM_001130692.2	c.59-70589C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CA	ENST00000394854.8	c.59-70589C>T		intron_variant		1	NM_000944.5	P3

Frequencies

GnomAD3 genomes AF: 0.00439 AC: 668 AN: 152096 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0000966

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.0592

Gnomad SAS AF: 0.00373

Gnomad FIN AF: 0.0120

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000338

Gnomad OTH AF: 0.00383

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

GnomAD4 genome AF: 0.00443 AC: 674 AN: 152214 Hom.: 15 Cov.: 32 AF XY: 0.00504 AC XY: 375 AN XY: 74428

Gnomad4 AFR AF: 0.0000963

Gnomad4 AMR AF: 0.0117

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.0597

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0120

Gnomad4 NFE AF: 0.000338

Gnomad4 OTH AF: 0.00379

Alfa AF: 0.00233 Hom.: 1

Bravo AF: 0.00566

Asia WGS AF: 0.0240 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.9
DANN	Benign	0.46

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: rs3804423; hg19: chr4-102187862;