rs2443504

Variant names:

• chr8-22519506-G-A
• rs2443504
• NM_005605.5:c.771-2985G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-22519506-G-A
• chr8-22519506-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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=-0.62).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.432 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CC	NM_005605.5	MANE Select	c.771-2985G>A		intron	N/A	NP_005596.2
	PPP3CC	NM_001243974.2		c.771-2985G>A		intron	N/A	NP_001230903.1
	PPP3CC	NM_001243975.2		c.771-2985G>A		intron	N/A	NP_001230904.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CC	ENST00000240139.10	TSL:1 MANE Select	c.771-2985G>A		intron	N/A	ENSP00000240139.5
	PPP3CC	ENST00000289963.12	TSL:1	c.771-2985G>A		intron	N/A	ENSP00000289963.8
	PPP3CC	ENST00000397775.7	TSL:2	c.771-2985G>A		intron	N/A	ENSP00000380878.3

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

African (AFR) AF: 0.0721 AC: 2988 AN: 41450

American (AMR) AF: 0.351 AC: 5355 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.379 AC: 1315 AN: 3472

East Asian (EAS) AF: 0.447 AC: 2308 AN: 5162

South Asian (SAS) AF: 0.326 AC: 1571 AN: 4824

European-Finnish (FIN) AF: 0.316 AC: 3316 AN: 10504

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.354 AC: 24041 AN: 67942

Other (OTH) AF: 0.276 AC: 582 AN: 2108

Alfa AF: 0.318 Hom.: 3137

Bravo AF: 0.270

Asia WGS AF: 0.321 AC: 1114 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	5.8
DANN	Benign	0.84
PhyloP100		0.76
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: rs2443504; hg19: chr8-22377019;