rs1482337

Positions:

• chr8-22537996-G-A
• chr8-22537996-G-T

Variant summary

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

The NM_005605.5(PPP3CC):​c.1322-1473G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.521 in 152,052 control chromosomes in the GnomAD database, including 21,383 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 0.52 (21383 hom., cov: 32)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.281

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=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.1322-1473G>A		intron_variant		ENST00000240139.10	NP_005596.2
LOC124901905	XR_007060851.1	n.1964+14166C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.1322-1473G>A		intron_variant		1	NM_005605.5	ENSP00000240139	P3
	ENST00000664810.1	n.93+15356C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.521 AC: 79168 AN: 151934 Hom.: 21357 Cov.: 32

Gnomad AFR AF: 0.677

Gnomad AMI AF: 0.541

Gnomad AMR AF: 0.491

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.537

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.449

Gnomad OTH AF: 0.474

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

GnomAD4 genome AF: 0.521 AC: 79242 AN: 152052 Hom.: 21383 Cov.: 32 AF XY: 0.520 AC XY: 38646 AN XY: 74324

Gnomad4 AFR AF: 0.678

Gnomad4 AMR AF: 0.491

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.497

Gnomad4 FIN AF: 0.433

Gnomad4 NFE AF: 0.449

Gnomad4 OTH AF: 0.472

Alfa AF: 0.492 Hom.: 3032

Bravo AF: 0.531

Asia WGS AF: 0.499 AC: 1734 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.73

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: rs1482337; hg19: chr8-22395509;