8-22503739-A-G

Variant names:

• chr8-22503739-A-G
• rs2461491
• NM_005605.5:c.484+5627A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005605.5(PPP3CC):​c.484+5627A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,972 control chromosomes in the GnomAD database, including 17,968 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 0.48 (17968 hom., cov: 32)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 12 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 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.484+5627A>G		intron	N/A	NP_005596.2
	PPP3CC	NM_001243974.2		c.484+5627A>G		intron	N/A	NP_001230903.1	P48454-3
	PPP3CC	NM_001243975.2		c.484+5627A>G		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.484+5627A>G		intron	N/A	ENSP00000240139.5	P48454-1
	PPP3CC	ENST00000289963.12	TSL:1	c.484+5627A>G		intron	N/A	ENSP00000289963.8	P48454-2
	PPP3CC	ENST00000968566.1		c.484+5627A>G		intron	N/A	ENSP00000638625.1

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73638 AN: 151854 Hom.: 17972 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.485 AC: 73665 AN: 151972 Hom.: 17968 Cov.: 32 AF XY: 0.485 AC XY: 36058 AN XY: 74282

African (AFR) AF: 0.529 AC: 21944 AN: 41454

American (AMR) AF: 0.475 AC: 7244 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.491 AC: 1701 AN: 3466

East Asian (EAS) AF: 0.603 AC: 3125 AN: 5180

South Asian (SAS) AF: 0.492 AC: 2368 AN: 4812

European-Finnish (FIN) AF: 0.442 AC: 4657 AN: 10540

Middle Eastern (MID) AF: 0.476 AC: 140 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31027 AN: 67954

Other (OTH) AF: 0.458 AC: 966 AN: 2110

Alfa AF: 0.465 Hom.: 9172

Bravo AF: 0.489

Asia WGS AF: 0.502 AC: 1741 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.36
PhyloP100		-1.1
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: rs2461491; hg19: chr8-22361252;