8-22540901-G-A

Variant names:

• chr8-22540901-G-A
• rs7430
• NM_005605.5:c.*99G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005605.5(PPP3CC):​c.*99G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000704 in 993,680 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.0000070 (0 hom.)
• Consequence: PPP3CC NM_005605.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.821
• Publications: 29 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CC	NM_005605.5	c.*99G>A		3_prime_UTR_variant	Exon 14 of 14	ENST00000240139.10	NP_005596.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CC	ENST00000240139.10	c.*99G>A		3_prime_UTR_variant	Exon 14 of 14	1	NM_005605.5	ENSP00000240139.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000704 AC: 7 AN: 993680 Hom.: 0 Cov.: 13 AF XY: 0.00000617 AC XY: 3 AN XY: 486314

African (AFR) AF: 0.00 AC: 0 AN: 22020

American (AMR) AF: 0.00 AC: 0 AN: 14510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16360

East Asian (EAS) AF: 0.00 AC: 0 AN: 30820

South Asian (SAS) AF: 0.00 AC: 0 AN: 41778

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29188

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3500

European-Non Finnish (NFE) AF: 0.00000883 AC: 7 AN: 792556

Other (OTH) AF: 0.00 AC: 0 AN: 42948

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 921

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	11
DANN	Benign	0.86
PhyloP100		0.82

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: rs7430; hg19: chr8-22398414;