rs2469770

chr8-22522343-G-Achr8-22522343-G-C

Variant summary

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

The NM_005605.5(PPP3CC):c.771-148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 614,018 control chromosomes in the GnomAD database, including 63,572 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 0.43 (14562 hom., cov: 32)
  • Exomes 𝑓: 0.46 (49010 hom.)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34

Genes affected

PPP3CC (HGNC:9316): (protein phosphatase 3 catalytic subunit gamma) Calcineurin is a calcium-dependent, calmodulin-stimulated protein phosphatase involved in the downstream regulation of dopaminergic signal transduction. Calcineurin is composed of a regulatory subunit and a catalytic subunit. The protein encoded by this gene represents one of the regulatory subunits that has been found for calcineurin. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3CC	NM_005605.5	c.771-148G>A		intron_variant		ENST00000240139.10
LOC124901905	XR_007060851.1	n.1964+29819C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CC	ENST00000240139.10	c.771-148G>A		intron_variant		1	NM_005605.5	P3
	ENST00000664810.1	n.93+31009C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66025 AN: 151748 Hom.: 14570 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.456 AC: 210905 AN: 462152 Hom.: 49010 AF XY: 0.457 AC XY: 112031 AN XY: 245072

Gnomad4 AFR exome AF: 0.377

Gnomad4 AMR exome AF: 0.456

Gnomad4 ASJ exome AF: 0.492

Gnomad4 EAS exome AF: 0.597

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.444

Gnomad4 OTH exome AF: 0.445

GnomAD4 genome AF: 0.435 AC: 66038 AN: 151866 Hom.: 14562 Cov.: 32 AF XY: 0.438 AC XY: 32517 AN XY: 74242

Gnomad4 AFR AF: 0.377

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.597

Gnomad4 SAS AF: 0.489

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.447

Gnomad4 OTH AF: 0.418

Alfa AF: 0.436 Hom.: 2375

Bravo AF: 0.432

Asia WGS AF: 0.494 AC: 1712 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.26
Dann	Benign	0.54

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: rs2469770; hg19: chr8-22379856;