rs2272080

Positions:

• chr8-22441213-T-G

Variant summary

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

The NM_005605.5(PPP3CC):​c.-197T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 462,214 control chromosomes in the GnomAD database, including 5,995 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 0.17 (4433 hom., cov: 33)
  • Exomes 𝑓: 0.075 (1562 hom.)
• Consequence: PPP3CC NM_005605.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.-197T>G		5_prime_UTR_variant	1/14	ENST00000240139.10	NP_005596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.-197T>G		5_prime_UTR_variant	1/14	1	NM_005605.5	ENSP00000240139	P3
PPP3CC	ENST00000289963.12	c.-197T>G		5_prime_UTR_variant	1/13	1		ENSP00000289963	A1
PPP3CC	ENST00000397775.7	c.-197T>G		5_prime_UTR_variant	1/15	2		ENSP00000380878
PPP3CC	ENST00000518852.5	c.-197T>G		5_prime_UTR_variant	1/8	2		ENSP00000429379

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26480 AN: 151948 Hom.: 4408 Cov.: 33

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0556

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.0751 AC: 23296 AN: 310158 Hom.: 1562 Cov.: 4 AF XY: 0.0740 AC XY: 12000 AN XY: 162068

Gnomad4 AFR exome AF: 0.434

Gnomad4 AMR exome AF: 0.114

Gnomad4 ASJ exome AF: 0.0664

Gnomad4 EAS exome AF: 0.142

Gnomad4 SAS exome AF: 0.0983

Gnomad4 FIN exome AF: 0.0393

Gnomad4 NFE exome AF: 0.0536

Gnomad4 OTH exome AF: 0.0995

GnomAD4 genome AF: 0.175 AC: 26565 AN: 152056 Hom.: 4433 Cov.: 33 AF XY: 0.170 AC XY: 12673 AN XY: 74350

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.0637

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.133

Gnomad4 FIN AF: 0.0391

Gnomad4 NFE AF: 0.0556

Gnomad4 OTH AF: 0.148

Alfa AF: 0.131 Hom.: 306

Bravo AF: 0.194

Asia WGS AF: 0.204 AC: 705 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs2272080; hg19: chr8-22298726;