8-22463293-G-A

Variant names:

• chr8-22463293-G-A
• rs10108011
• NM_005605.5:c.50-11661G>A

Variant summary

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

The NM_005605.5(PPP3CC):​c.50-11661G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.63 in 152,100 control chromosomes in the GnomAD database, including 31,051 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 0.63 (31051 hom., cov: 32)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.370
• Publications: 17 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)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.779 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.50-11661G>A		intron	N/A	NP_005596.2
	PPP3CC	NM_001243974.2		c.50-11661G>A		intron	N/A	NP_001230903.1
	PPP3CC	NM_001243975.2		c.50-11661G>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.50-11661G>A		intron	N/A	ENSP00000240139.5
	PPP3CC	ENST00000289963.12	TSL:1	c.50-11661G>A		intron	N/A	ENSP00000289963.8
	PPP3CC	ENST00000397775.7	TSL:2	c.50-11661G>A		intron	N/A	ENSP00000380878.3

Frequencies

GnomAD3 genomes AF: 0.630 AC: 95782 AN: 151982 Hom.: 31003 Cov.: 32

Gnomad AFR AF: 0.786

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.579

Gnomad ASJ AF: 0.574

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.611

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.564

Gnomad NFE AF: 0.555

Gnomad OTH AF: 0.584

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

GnomAD4 genome AF: 0.630 AC: 95880 AN: 152100 Hom.: 31051 Cov.: 32 AF XY: 0.629 AC XY: 46775 AN XY: 74356

African (AFR) AF: 0.786 AC: 32621 AN: 41508

American (AMR) AF: 0.579 AC: 8843 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.574 AC: 1989 AN: 3468

East Asian (EAS) AF: 0.762 AC: 3938 AN: 5166

South Asian (SAS) AF: 0.611 AC: 2950 AN: 4832

European-Finnish (FIN) AF: 0.559 AC: 5910 AN: 10574

Middle Eastern (MID) AF: 0.568 AC: 166 AN: 292

European-Non Finnish (NFE) AF: 0.554 AC: 37683 AN: 67960

Other (OTH) AF: 0.588 AC: 1242 AN: 2114

Alfa AF: 0.570 Hom.: 29150

Bravo AF: 0.636

Asia WGS AF: 0.718 AC: 2496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.0
DANN	Benign	0.71
PhyloP100		-0.37
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: rs10108011; hg19: chr8-22320806;