rs2461489

Positions:

• chr8-22512740-G-A
• chr8-22512740-G-T

Variant summary

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

The NM_005605.5(PPP3CC):​c.631-553G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,924 control chromosomes in the GnomAD database, including 14,047 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 (14047 hom., cov: 32)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.415

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.631-553G>A		intron_variant		ENST00000240139.10	NP_005596.2
LOC124901905	XR_007060851.1	n.1965-30011C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.631-553G>A		intron_variant		1	NM_005605.5	ENSP00000240139	P3
	ENST00000664810.1	n.94-30011C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64843 AN: 151808 Hom.: 14055 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.539

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.553

Gnomad SAS AF: 0.488

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.413

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

GnomAD4 genome AF: 0.427 AC: 64852 AN: 151924 Hom.: 14047 Cov.: 32 AF XY: 0.430 AC XY: 31930 AN XY: 74208

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.452

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.552

Gnomad4 SAS AF: 0.488

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.446

Gnomad4 OTH AF: 0.412

Alfa AF: 0.442 Hom.: 6649

Bravo AF: 0.423

Asia WGS AF: 0.480 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.75

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: rs2461489; hg19: chr8-22370253;