8-22440959-T-G

Position:

• chr8-22440959-T-G

Variant summary

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

The ENST00000518852.5(PPP3CC):​c.-451T>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 0.174 in 154,198 control chromosomes in the GnomAD database, including 4,387 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 0.18 (4361 hom., cov: 33)
  • Exomes 𝑓: 0.071 (26 hom.)
• Consequence: PPP3CC ENST00000518852.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88

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=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PPP3CC	ENST00000518852.5	c.-451T>G		5_prime_UTR_variant	1/8	2

Frequencies

GnomAD3 genomes AF: 0.176 AC: 26360 AN: 149486 Hom.: 4336 Cov.: 33

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.0100

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.0642

Gnomad EAS AF: 0.200

Gnomad SAS AF: 0.145

Gnomad FIN AF: 0.0406

Gnomad MID AF: 0.0962

Gnomad NFE AF: 0.0562

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.0709 AC: 325 AN: 4582 Hom.: 26 Cov.: 0 AF XY: 0.0699 AC XY: 165 AN XY: 2360

Gnomad4 AFR exome AF: 0.459

Gnomad4 AMR exome AF: 0.0915

Gnomad4 ASJ exome AF: 0.0680

Gnomad4 EAS exome AF: 0.103

Gnomad4 SAS exome AF: 0.0769

Gnomad4 FIN exome AF: 0.0284

Gnomad4 NFE exome AF: 0.0468

Gnomad4 OTH exome AF: 0.0828

GnomAD4 genome AF: 0.177 AC: 26445 AN: 149616 Hom.: 4361 Cov.: 33 AF XY: 0.173 AC XY: 12620 AN XY: 73122

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.0642

Gnomad4 EAS AF: 0.200

Gnomad4 SAS AF: 0.143

Gnomad4 FIN AF: 0.0406

Gnomad4 NFE AF: 0.0562

Gnomad4 OTH AF: 0.148

Alfa AF: 0.0447 Hom.: 78

Bravo AF: 0.194

Asia WGS AF: 0.203 AC: 701 AN: 3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	4.8
DANN	Benign	0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs9886594; hg19: chr8-22298472;