rs2469770

Variant names:

• chr8-22522343-G-A
• rs2469770
• NM_005605.5:c.771-148G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-22522343-G-A
• chr8-22522343-G-C
• chr8-22522343-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005605.5(PPP3CC):​c.771-148G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 614,018 control chromosomes in the GnomAD database, including 63,572 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 0.43 (14562 hom., cov: 32)
  • Exomes 𝑓: 0.46 (49010 hom.)
• Consequence: PPP3CC NM_005605.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 7 publications found

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]

PPP3CC Gene-Disease associations (from GenCC):

• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000251034 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005605.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CC	NM_005605.5	MANE Select	c.771-148G>A		intron	N/A	NP_005596.2
	PPP3CC	NM_001243974.2		c.771-148G>A		intron	N/A	NP_001230903.1	P48454-3
	PPP3CC	NM_001243975.2		c.771-148G>A		intron	N/A	NP_001230904.1	P48454-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CC	ENST00000240139.10	TSL:1 MANE Select	c.771-148G>A		intron	N/A	ENSP00000240139.5	P48454-1
	PPP3CC	ENST00000289963.12	TSL:1	c.771-148G>A		intron	N/A	ENSP00000289963.8	P48454-2
	PPP3CC	ENST00000968566.1		c.771-148G>A		intron	N/A	ENSP00000638625.1

Frequencies

GnomAD3 genomes AF: 0.435 AC: 66025 AN: 151748 Hom.: 14570 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.538

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.598

Gnomad SAS AF: 0.489

Gnomad FIN AF: 0.433

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.447

Gnomad OTH AF: 0.419

GnomAD4 exome AF: 0.456 AC: 210905 AN: 462152 Hom.: 49010 AF XY: 0.457 AC XY: 112031 AN XY: 245072

African (AFR) AF: 0.377 AC: 4780 AN: 12688

American (AMR) AF: 0.456 AC: 8222 AN: 18026

Ashkenazi Jewish (ASJ) AF: 0.492 AC: 6822 AN: 13852

East Asian (EAS) AF: 0.597 AC: 18464 AN: 30924

South Asian (SAS) AF: 0.467 AC: 20297 AN: 43484

European-Finnish (FIN) AF: 0.438 AC: 13761 AN: 31434

Middle Eastern (MID) AF: 0.486 AC: 960 AN: 1974

European-Non Finnish (NFE) AF: 0.444 AC: 125867 AN: 283396

Other (OTH) AF: 0.445 AC: 11732 AN: 26374

GnomAD4 genome AF: 0.435 AC: 66038 AN: 151866 Hom.: 14562 Cov.: 32 AF XY: 0.438 AC XY: 32517 AN XY: 74242

African (AFR) AF: 0.377 AC: 15598 AN: 41392

American (AMR) AF: 0.452 AC: 6903 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1695 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3088 AN: 5172

South Asian (SAS) AF: 0.489 AC: 2357 AN: 4820

European-Finnish (FIN) AF: 0.433 AC: 4565 AN: 10532

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.447 AC: 30323 AN: 67912

Other (OTH) AF: 0.418 AC: 881 AN: 2108

Alfa AF: 0.433 Hom.: 2426

Bravo AF: 0.432

Asia WGS AF: 0.494 AC: 1712 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.26
DANN	Benign	0.54
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2469770; hg19: chr8-22379856;