chr8-22537407-A-G

Variant names:

• chr8-22537407-A-G
• rs1116085
• NM_005605.5:c.1322-2062A>G

Variant summary

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

The NM_001243974.2(PPP3CC):​c.1349-2062A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.459 in 152,028 control chromosomes in the GnomAD database, including 16,127 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 0.46 (16127 hom., cov: 32)
• Consequence: PPP3CC NM_001243974.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243974.2. 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.1322-2062A>G		intron	N/A	NP_005596.2
	PPP3CC	NM_001243974.2		c.1349-2062A>G		intron	N/A	NP_001230903.1
	PPP3CC	NM_001243975.2		c.1322-3208A>G		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.1322-2062A>G		intron	N/A	ENSP00000240139.5
	PPP3CC	ENST00000289963.12	TSL:1	c.1322-3208A>G		intron	N/A	ENSP00000289963.8
	PPP3CC	ENST00000968566.1		c.1322-2325A>G		intron	N/A	ENSP00000638625.1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69807 AN: 151910 Hom.: 16131 Cov.: 32

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.489

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.497

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.468

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.459 AC: 69829 AN: 152028 Hom.: 16127 Cov.: 32 AF XY: 0.461 AC XY: 34302 AN XY: 74328

African (AFR) AF: 0.458 AC: 19002 AN: 41458

American (AMR) AF: 0.466 AC: 7117 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.489 AC: 1696 AN: 3466

East Asian (EAS) AF: 0.589 AC: 3039 AN: 5160

South Asian (SAS) AF: 0.496 AC: 2395 AN: 4824

European-Finnish (FIN) AF: 0.433 AC: 4571 AN: 10568

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

European-Non Finnish (NFE) AF: 0.448 AC: 30459 AN: 67952

Other (OTH) AF: 0.435 AC: 917 AN: 2108

Alfa AF: 0.453 Hom.: 58687

Bravo AF: 0.461

Asia WGS AF: 0.493 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.86
PhyloP100		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: rs1116085; hg19: chr8-22394920;