rs2443504

Positions:

• chr8-22519506-G-A
• chr8-22519506-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.771-2985G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.276 in 151,936 control chromosomes in the GnomAD database, including 7,127 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 0.28 (7127 hom., cov: 32)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.763

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]

ENSG00000251034 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.771-2985G>A		intron_variant		ENST00000240139.10	NP_005596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.771-2985G>A		intron_variant		1	NM_005605.5	ENSP00000240139.5

Frequencies

GnomAD3 genomes AF: 0.277 AC: 41987 AN: 151816 Hom.: 7136 Cov.: 32

Gnomad AFR AF: 0.0723

Gnomad AMI AF: 0.427

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.379

Gnomad EAS AF: 0.447

Gnomad SAS AF: 0.325

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.278

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

GnomAD4 genome AF: 0.276 AC: 41974 AN: 151936 Hom.: 7127 Cov.: 32 AF XY: 0.279 AC XY: 20698 AN XY: 74256

Gnomad4 AFR AF: 0.0721

Gnomad4 AMR AF: 0.351

Gnomad4 ASJ AF: 0.379

Gnomad4 EAS AF: 0.447

Gnomad4 SAS AF: 0.326

Gnomad4 FIN AF: 0.316

Gnomad4 NFE AF: 0.354

Gnomad4 OTH AF: 0.276

Alfa AF: 0.313 Hom.: 1928

Bravo AF: 0.270

Asia WGS AF: 0.321 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.8
DANN	Benign	0.84

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: rs2443504; hg19: chr8-22377019;