8-22528966-C-T

Variant names:

• chr8-22528966-C-T
• rs2461483
• NM_005605.5:c.1141+389C>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.1141+389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,852 control chromosomes in the GnomAD database, including 25,032 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 (25032 hom., cov: 31)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132
• Publications: 13 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 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.1141+389C>T		intron	N/A	NP_005596.2
	PPP3CC	NM_001243974.2		c.1141+389C>T		intron	N/A	NP_001230903.1	P48454-3
	PPP3CC	NM_001243975.2		c.1141+389C>T		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.1141+389C>T		intron	N/A	ENSP00000240139.5	P48454-1
	PPP3CC	ENST00000289963.12	TSL:1	c.1141+389C>T		intron	N/A	ENSP00000289963.8	P48454-2
	PPP3CC	ENST00000968566.1		c.1141+389C>T		intron	N/A	ENSP00000638625.1

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84686 AN: 151732 Hom.: 24981 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.558 AC: 84795 AN: 151852 Hom.: 25032 Cov.: 31 AF XY: 0.557 AC XY: 41343 AN XY: 74220

African (AFR) AF: 0.767 AC: 31769 AN: 41434

American (AMR) AF: 0.525 AC: 8007 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.513 AC: 1778 AN: 3466

East Asian (EAS) AF: 0.617 AC: 3191 AN: 5172

South Asian (SAS) AF: 0.520 AC: 2508 AN: 4820

European-Finnish (FIN) AF: 0.447 AC: 4691 AN: 10500

Middle Eastern (MID) AF: 0.490 AC: 143 AN: 292

European-Non Finnish (NFE) AF: 0.459 AC: 31133 AN: 67896

Other (OTH) AF: 0.515 AC: 1084 AN: 2106

Alfa AF: 0.472 Hom.: 21590

Bravo AF: 0.573

Asia WGS AF: 0.569 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.7
DANN	Benign	0.63
PhyloP100		0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs2461483; hg19: chr8-22386479;