rs2469758

Variant names:

• chr8-22505519-C-T
• rs2469758
• NM_005605.5:c.485-5567C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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]

PPP3CC Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000251034 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.485-5567C>T		intron_variant	Intron 4 of 13	ENST00000240139.10	NP_005596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.485-5567C>T		intron_variant	Intron 4 of 13	1	NM_005605.5	ENSP00000240139.5

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

African (AFR) AF: 0.341 AC: 14120 AN: 41390

American (AMR) AF: 0.455 AC: 6936 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.494 AC: 1715 AN: 3470

East Asian (EAS) AF: 0.600 AC: 3106 AN: 5176

South Asian (SAS) AF: 0.493 AC: 2367 AN: 4802

European-Finnish (FIN) AF: 0.445 AC: 4673 AN: 10510

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.463 AC: 31489 AN: 67944

Other (OTH) AF: 0.418 AC: 882 AN: 2108

Alfa AF: 0.451 Hom.: 5355

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
PhyloP100		-0.057
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2469758; hg19: chr8-22363032;