chr8-22528966-C-T

Position:

• chr8-22528966-C-T

Variant summary

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

The NM_005605.5(PPP3CC):​c.1141+389C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.558 in 151,852 control chromosomes in the GnomAD database, including 25,032 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 0.56 (25032 hom., cov: 31)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.132

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.1141+389C>T		intron_variant		ENST00000240139.10	NP_005596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.1141+389C>T		intron_variant		1	NM_005605.5	ENSP00000240139.5

Frequencies

GnomAD3 genomes AF: 0.558 AC: 84686 AN: 151732 Hom.: 24981 Cov.: 31

Gnomad AFR AF: 0.766

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.525

Gnomad ASJ AF: 0.513

Gnomad EAS AF: 0.617

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.447

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.459

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.558 AC: 84795 AN: 151852 Hom.: 25032 Cov.: 31 AF XY: 0.557 AC XY: 41343 AN XY: 74220

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.525

Gnomad4 ASJ AF: 0.513

Gnomad4 EAS AF: 0.617

Gnomad4 SAS AF: 0.520

Gnomad4 FIN AF: 0.447

Gnomad4 NFE AF: 0.459

Gnomad4 OTH AF: 0.515

Alfa AF: 0.471 Hom.: 18884

Bravo AF: 0.573

Asia WGS AF: 0.569 AC: 1976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.7
DANN	Benign	0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs2461483; hg19: chr8-22386479;