rs896379

Variant names:

• chr8-22516687-G-A
• rs896379
• NM_005605.5:c.770+3255G>A

Variant summary

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

The ENST00000240139.10(PPP3CC):​c.770+3255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,016 control chromosomes in the GnomAD database, including 24,609 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 0.55 (24609 hom., cov: 32)
• Consequence: PPP3CC ENST00000240139.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257
• Publications: 11 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000240139.10. 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.770+3255G>A		intron	N/A	NP_005596.2
	PPP3CC	NM_001243974.2		c.770+3255G>A		intron	N/A	NP_001230903.1
	PPP3CC	NM_001243975.2		c.770+3255G>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.770+3255G>A		intron	N/A	ENSP00000240139.5
	PPP3CC	ENST00000289963.12	TSL:1	c.770+3255G>A		intron	N/A	ENSP00000289963.8
	PPP3CC	ENST00000397775.7	TSL:2	c.770+3255G>A		intron	N/A	ENSP00000380878.3

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83933 AN: 151898 Hom.: 24561 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.553 AC: 84038 AN: 152016 Hom.: 24609 Cov.: 32 AF XY: 0.551 AC XY: 40940 AN XY: 74278

African (AFR) AF: 0.761 AC: 31539 AN: 41456

American (AMR) AF: 0.523 AC: 7989 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 1756 AN: 3470

East Asian (EAS) AF: 0.646 AC: 3340 AN: 5170

South Asian (SAS) AF: 0.518 AC: 2500 AN: 4822

European-Finnish (FIN) AF: 0.434 AC: 4578 AN: 10546

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.451 AC: 30627 AN: 67954

Other (OTH) AF: 0.506 AC: 1066 AN: 2108

Alfa AF: 0.485 Hom.: 71209

Bravo AF: 0.568

Asia WGS AF: 0.576 AC: 2002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.52
PhyloP100		-0.26
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: rs896379; hg19: chr8-22374200;