chr8-22537407-A-G

Position:

• chr8-22537407-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005605.5(PPP3CC):​c.1322-2062A>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_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.05

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3CC	NM_005605.5	c.1322-2062A>G		intron_variant		ENST00000240139.10
LOC124901905	XR_007060851.1	n.1964+14755T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CC	ENST00000240139.10	c.1322-2062A>G		intron_variant		1	NM_005605.5	P3
	ENST00000664810.1	n.93+15945T>C		intron_variant, non_coding_transcript_variant

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

Gnomad4 AFR AF: 0.458

Gnomad4 AMR AF: 0.466

Gnomad4 ASJ AF: 0.489

Gnomad4 EAS AF: 0.589

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.448

Gnomad4 OTH AF: 0.435

Alfa AF: 0.452 Hom.: 26142

Bravo AF: 0.461

Asia WGS AF: 0.493 AC: 1712 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	14
DANN	Benign	0.86

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

Publications

LitVar

Other links and lift over

dbSNP: rs1116085; hg19: chr8-22394920;