8-22537796-C-T

Variant names:

• chr8-22537796-C-T
• rs1116084
• NM_005605.5:c.1322-1673C>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.1322-1673C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.436 in 151,966 control chromosomes in the GnomAD database, including 14,547 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 0.44 (14547 hom., cov: 33)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.1322-1673C>T		intron_variant	Intron 12 of 13	ENST00000240139.10	NP_005596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.1322-1673C>T		intron_variant	Intron 12 of 13	1	NM_005605.5	ENSP00000240139.5

Frequencies

GnomAD3 genomes AF: 0.436 AC: 66185 AN: 151848 Hom.: 14553 Cov.: 33

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.535

Gnomad SAS AF: 0.494

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.415

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

GnomAD4 genome AF: 0.436 AC: 66207 AN: 151966 Hom.: 14547 Cov.: 33 AF XY: 0.438 AC XY: 32511 AN XY: 74280

African (AFR) AF: 0.385 AC: 15936 AN: 41440

American (AMR) AF: 0.456 AC: 6968 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1698 AN: 3472

East Asian (EAS) AF: 0.535 AC: 2759 AN: 5160

South Asian (SAS) AF: 0.493 AC: 2375 AN: 4816

European-Finnish (FIN) AF: 0.433 AC: 4570 AN: 10562

Middle Eastern (MID) AF: 0.480 AC: 141 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30400 AN: 67938

Other (OTH) AF: 0.413 AC: 870 AN: 2104

Alfa AF: 0.444 Hom.: 57548

Bravo AF: 0.434

Asia WGS AF: 0.472 AC: 1639 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	9.1
DANN	Benign	0.81
PhyloP100		-0.094
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: rs1116084; hg19: chr8-22395309;