rs2469758

chr8-22505519-C-T

Variant summary

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

The NM_005605.5(PPP3CC):c.485-5567C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 151,846 control chromosomes in the GnomAD database, including 14,650 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 (14650 hom., cov: 31)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570

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 = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3CC	NM_005605.5	c.485-5567C>T		intron_variant		ENST00000240139.10
LOC124901905	XR_007060851.1	n.1965-22790G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CC	ENST00000240139.10	c.485-5567C>T		intron_variant		1	NM_005605.5	P3
	ENST00000664810.1	n.94-22790G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65913 AN: 151728 Hom.: 14660 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.546

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.601

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.419

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

GnomAD4 genome AF: 0.434 AC: 65922 AN: 151846 Hom.: 14650 Cov.: 31 AF XY: 0.437 AC XY: 32398 AN XY: 74200

Gnomad4 AFR AF: 0.341

Gnomad4 AMR AF: 0.455

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.493

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.463

Gnomad4 OTH AF: 0.418

Alfa AF: 0.451 Hom.: 3201

Bravo AF: 0.429

Asia WGS AF: 0.499 AC: 1732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.1
Dann	Benign	0.67

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: rs2469758; hg19: chr8-22363032;