rs2461489

Variant names:

• chr8-22512740-G-A
• rs2461489
• NM_005605.5:c.631-553G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-22512740-G-A
• chr8-22512740-G-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.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
• Publications: 7 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005605.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CC	NM_005605.5	MANE Select	c.631-553G>A		intron	N/A	NP_005596.2
	PPP3CC	NM_001243974.2		c.631-553G>A		intron	N/A	NP_001230903.1	P48454-3
	PPP3CC	NM_001243975.2		c.631-553G>A		intron	N/A	NP_001230904.1	P48454-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CC	ENST00000240139.10	TSL:1 MANE Select	c.631-553G>A		intron	N/A	ENSP00000240139.5	P48454-1
	PPP3CC	ENST00000289963.12	TSL:1	c.631-553G>A		intron	N/A	ENSP00000289963.8	P48454-2
	PPP3CC	ENST00000968566.1		c.631-553G>A		intron	N/A	ENSP00000638625.1

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

African (AFR) AF: 0.354 AC: 14670 AN: 41434

American (AMR) AF: 0.452 AC: 6898 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1694 AN: 3464

East Asian (EAS) AF: 0.552 AC: 2851 AN: 5166

South Asian (SAS) AF: 0.488 AC: 2352 AN: 4822

European-Finnish (FIN) AF: 0.433 AC: 4557 AN: 10516

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.446 AC: 30337 AN: 67952

Other (OTH) AF: 0.412 AC: 867 AN: 2102

Alfa AF: 0.442 Hom.: 7500

Bravo AF: 0.423

Asia WGS AF: 0.480 AC: 1667 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.7
DANN	Benign	0.75
PhyloP100		-0.41
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: rs2461489; hg19: chr8-22370253;