rs896379

Positions:

• chr8-22516687-G-A

Variant summary

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

The NM_005605.5(PPP3CC):​c.770+3255G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.553 in 152,016 control chromosomes in the GnomAD database, including 24,609 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 0.55 (24609 hom., cov: 32)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.257

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PPP3CC	NM_005605.5	c.770+3255G>A		intron_variant		ENST00000240139.10
LOC124901905	XR_007060851.1	n.1965-33958C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CC	ENST00000240139.10	c.770+3255G>A		intron_variant		1	NM_005605.5	P3
	ENST00000664810.1	n.94-33958C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83933 AN: 151898 Hom.: 24561 Cov.: 32

Gnomad AFR AF: 0.760

Gnomad AMI AF: 0.540

Gnomad AMR AF: 0.523

Gnomad ASJ AF: 0.506

Gnomad EAS AF: 0.646

Gnomad SAS AF: 0.519

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.451

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.553 AC: 84038 AN: 152016 Hom.: 24609 Cov.: 32 AF XY: 0.551 AC XY: 40940 AN XY: 74278

Gnomad4 AFR AF: 0.761

Gnomad4 AMR AF: 0.523

Gnomad4 ASJ AF: 0.506

Gnomad4 EAS AF: 0.646

Gnomad4 SAS AF: 0.518

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.451

Gnomad4 OTH AF: 0.506

Alfa AF: 0.470 Hom.: 28452

Bravo AF: 0.568

Asia WGS AF: 0.576 AC: 2002 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.77
DANN	Benign	0.52

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: rs896379; hg19: chr8-22374200;