8-22513381-C-G

Variant names:

• chr8-22513381-C-G
• rs199697260
• NM_005605.5:c.719C>G

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.719C>G​(p.Thr240Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T240I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP3CC NM_005605.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12
• Publications: 1 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 (MetaRNN=0.10511765).

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.719C>G	p.Thr240Ser	missense	Exon 6 of 14	NP_005596.2
	PPP3CC	NM_001243974.2		c.719C>G	p.Thr240Ser	missense	Exon 6 of 15	NP_001230903.1	P48454-3
	PPP3CC	NM_001243975.2		c.719C>G	p.Thr240Ser	missense	Exon 6 of 13	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.719C>G	p.Thr240Ser	missense	Exon 6 of 14	ENSP00000240139.5	P48454-1
	PPP3CC	ENST00000289963.12	TSL:1	c.719C>G	p.Thr240Ser	missense	Exon 6 of 13	ENSP00000289963.8	P48454-2
	PPP3CC	ENST00000968566.1		c.719C>G	p.Thr240Ser	missense	Exon 6 of 14	ENSP00000638625.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	16
DANN	Benign	0.39
DEOGEN2	Benign	0.26	T
Eigen	Benign	-0.80
Eigen_PC	Benign	-0.63
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.40	N
PhyloP100		4.1
PrimateAI	Uncertain	0.55	T
PROVEAN	Benign	-1.3	N
REVEL	Benign	0.14
Sift	Benign	0.44	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.33
MutPred		0.30		Loss of phosphorylation at T240 (P = 0.0632)
MVP		0.41
MPC		0.27
ClinPred		0.43	T
GERP RS		4.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.072
gMVP		0.35
Mutation Taster		=75/25	polymorphism

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: rs199697260; hg19: chr8-22370894;