chr8-22503739-A-G

Position:

• chr8-22503739-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.484+5627A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.485 in 151,972 control chromosomes in the GnomAD database, including 17,968 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 0.48 (17968 hom., cov: 32)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10

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]

ENSG00000251034 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.586 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.484+5627A>G		intron_variant		ENST00000240139.10	NP_005596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.484+5627A>G		intron_variant		1	NM_005605.5	ENSP00000240139.5

Frequencies

GnomAD3 genomes AF: 0.485 AC: 73638 AN: 151854 Hom.: 17972 Cov.: 32

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.491

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.493

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.459

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

GnomAD4 genome AF: 0.485 AC: 73665 AN: 151972 Hom.: 17968 Cov.: 32 AF XY: 0.485 AC XY: 36058 AN XY: 74282

Gnomad4 AFR AF: 0.529

Gnomad4 AMR AF: 0.475

Gnomad4 ASJ AF: 0.491

Gnomad4 EAS AF: 0.603

Gnomad4 SAS AF: 0.492

Gnomad4 FIN AF: 0.442

Gnomad4 NFE AF: 0.457

Gnomad4 OTH AF: 0.458

Alfa AF: 0.465 Hom.: 8322

Bravo AF: 0.489

Asia WGS AF: 0.502 AC: 1741 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.27
DANN	Benign	0.36

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: rs2461491; hg19: chr8-22361252;