8-22532387-T-G

Variant names:

• chr8-22532387-T-G
• rs2449340
• NM_005605.5:c.1223+81T>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.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
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.763 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.1223+81T>G		intron	N/A	NP_005596.2
	PPP3CC	NM_001243974.2		c.1250+81T>G		intron	N/A	NP_001230903.1	P48454-3
	PPP3CC	NM_001243975.2		c.1223+81T>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.1223+81T>G		intron	N/A	ENSP00000240139.5	P48454-1
	PPP3CC	ENST00000289963.12	TSL:1	c.1223+81T>G		intron	N/A	ENSP00000289963.8	P48454-2
	PPP3CC	ENST00000968566.1		c.1223+81T>G		intron	N/A	ENSP00000638625.1

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

African (AFR) AF: 0.779 AC: 19294 AN: 24752

American (AMR) AF: 0.544 AC: 20219 AN: 37182

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 11484 AN: 22392

East Asian (EAS) AF: 0.686 AC: 25682 AN: 37456

South Asian (SAS) AF: 0.517 AC: 37656 AN: 72840

European-Finnish (FIN) AF: 0.438 AC: 21695 AN: 49570

Middle Eastern (MID) AF: 0.560 AC: 2736 AN: 4886

European-Non Finnish (NFE) AF: 0.456 AC: 347470 AN: 762640

Other (OTH) AF: 0.495 AC: 23235 AN: 46956

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

African (AFR) AF: 0.770 AC: 31948 AN: 41486

American (AMR) AF: 0.525 AC: 8019 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.511 AC: 1770 AN: 3462

East Asian (EAS) AF: 0.703 AC: 3632 AN: 5166

South Asian (SAS) AF: 0.532 AC: 2566 AN: 4826

European-Finnish (FIN) AF: 0.435 AC: 4593 AN: 10570

Middle Eastern (MID) AF: 0.524 AC: 153 AN: 292

European-Non Finnish (NFE) AF: 0.453 AC: 30828 AN: 67984

Other (OTH) AF: 0.511 AC: 1080 AN: 2114

Alfa AF: 0.521 Hom.: 3692

Bravo AF: 0.575

Asia WGS AF: 0.599 AC: 2080 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.50
PhyloP100		-0.30
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: rs2449340; hg19: chr8-22389900; COSMIC: COSV51502387; COSMIC: COSV51502387;