8-22500085-T-C

Variant names:

• chr8-22500085-T-C
• rs2469749
• NM_005605.5:c.484+1973T>C

Variant summary

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

The NM_005605.5(PPP3CC):​c.484+1973T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 152,020 control chromosomes in the GnomAD database, including 33,319 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 0.66 (33319 hom., cov: 32)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0320

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.484+1973T>C		intron_variant	Intron 4 of 13	ENST00000240139.10	NP_005596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.484+1973T>C		intron_variant	Intron 4 of 13	1	NM_005605.5	ENSP00000240139.5

Frequencies

GnomAD3 genomes AF: 0.661 AC: 100369 AN: 151902 Hom.: 33303 Cov.: 32

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.646

Gnomad EAS AF: 0.631

Gnomad SAS AF: 0.659

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.648

Gnomad OTH AF: 0.656

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

GnomAD4 genome AF: 0.661 AC: 100435 AN: 152020 Hom.: 33319 Cov.: 32 AF XY: 0.655 AC XY: 48681 AN XY: 74284

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.636

Gnomad4 ASJ AF: 0.646

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.659

Gnomad4 FIN AF: 0.547

Gnomad4 NFE AF: 0.648

Gnomad4 OTH AF: 0.653

Alfa AF: 0.652 Hom.: 45709

Bravo AF: 0.669

Asia WGS AF: 0.601 AC: 2090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	1.9
DANN	Benign	0.80

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: rs2469749; hg19: chr8-22357598;