8-22440959-T-C

Variant names:

• chr8-22440959-T-C
• rs9886594
• ENST00000518852.5:c.-451T>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000518852.5(PPP3CC):​c.-451T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP3CC ENST00000518852.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.88
• Publications: 2 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)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.-451T>C		upstream_gene_variant		ENST00000240139.10	NP_005596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000518852.5	c.-451T>C		5_prime_UTR_variant	Exon 1 of 8	2		ENSP00000429379.1
PPP3CC	ENST00000240139.10	c.-451T>C		upstream_gene_variant		1	NM_005605.5	ENSP00000240139.5
PPP3CC	ENST00000289963.12	c.-451T>C		upstream_gene_variant		1		ENSP00000289963.8
PPP3CC	ENST00000397775.7	c.-451T>C		upstream_gene_variant		2		ENSP00000380878.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4590 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2362

African (AFR) AF: 0.00 AC: 0 AN: 172

American (AMR) AF: 0.00 AC: 0 AN: 142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 206

East Asian (EAS) AF: 0.00 AC: 0 AN: 312

South Asian (SAS) AF: 0.00 AC: 0 AN: 52

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 24

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 3166

Other (OTH) AF: 0.00 AC: 0 AN: 340

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 78

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.1
DANN	Benign	0.50
PhyloP100		-1.9
PromoterAI		-0.0092	Neutral

Splicing

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

Other links and lift over

dbSNP: rs9886594; hg19: chr8-22298472;