rs2449340

Positions:

• chr8-22532387-T-G

Variant summary

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

The NM_005605.5(PPP3CC):​c.1223+81T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,210,768 control chromosomes in the GnomAD database, including 151,149 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 0.56 (25294 hom., cov: 33)
  • Exomes 𝑓: 0.48 (125855 hom.)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.1223+81T>G		intron_variant		ENST00000240139.10	NP_005596.2
LOC124901905	XR_007060851.1	n.1964+19775A>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.1223+81T>G		intron_variant		1	NM_005605.5	ENSP00000240139	P3
	ENST00000664810.1	n.93+20965A>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.559 AC: 84972 AN: 151976 Hom.: 25244 Cov.: 33

Gnomad AFR AF: 0.770

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.511

Gnomad EAS AF: 0.703

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.506

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.507

GnomAD4 exome AF: 0.481 AC: 509471 AN: 1058674 Hom.: 125855 AF XY: 0.481 AC XY: 260404 AN XY: 541170

Gnomad4 AFR exome AF: 0.779

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.513

Gnomad4 EAS exome AF: 0.686

Gnomad4 SAS exome AF: 0.517

Gnomad4 FIN exome AF: 0.438

Gnomad4 NFE exome AF: 0.456

Gnomad4 OTH exome AF: 0.495

GnomAD4 genome AF: 0.559 AC: 85079 AN: 152094 Hom.: 25294 Cov.: 33 AF XY: 0.559 AC XY: 41533 AN XY: 74364

Gnomad4 AFR AF: 0.770

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.511

Gnomad4 EAS AF: 0.703

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.511

Alfa AF: 0.513 Hom.: 3464

Bravo AF: 0.575

Asia WGS AF: 0.599 AC: 2080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.50

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: rs2449340; hg19: chr8-22389900; COSMIC: COSV51502387; COSMIC: COSV51502387;