chr8-22441213-T-G

Variant names:

• chr8-22441213-T-G
• rs2272080
• NM_005605.5:c.-197T>G

Variant summary

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

The NM_001243974.2(PPP3CC):​c.-197T>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 462,214 control chromosomes in the GnomAD database, including 5,995 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 0.17 (4433 hom., cov: 33)
  • Exomes 𝑓: 0.075 (1562 hom.)
• Consequence: PPP3CC NM_001243974.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0830
• Publications: 9 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001243974.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CC	NM_005605.5	MANE Select	c.-197T>G		5_prime_UTR	Exon 1 of 14	NP_005596.2
	PPP3CC	NM_001243974.2		c.-197T>G		5_prime_UTR	Exon 1 of 15	NP_001230903.1
	PPP3CC	NM_001243975.2		c.-197T>G		5_prime_UTR	Exon 1 of 13	NP_001230904.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CC	ENST00000240139.10	TSL:1 MANE Select	c.-197T>G		5_prime_UTR	Exon 1 of 14	ENSP00000240139.5
	PPP3CC	ENST00000289963.12	TSL:1	c.-197T>G		5_prime_UTR	Exon 1 of 13	ENSP00000289963.8
	PPP3CC	ENST00000968566.1		c.-197T>G		5_prime_UTR	Exon 1 of 14	ENSP00000638625.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26480 AN: 151948 Hom.: 4408 Cov.: 33

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.00989

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.0637

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.0955

Gnomad NFE AF: 0.0556

Gnomad OTH AF: 0.142

GnomAD4 exome AF: 0.0751 AC: 23296 AN: 310158 Hom.: 1562 Cov.: 4 AF XY: 0.0740 AC XY: 12000 AN XY: 162068

African (AFR) AF: 0.434 AC: 3094 AN: 7122

American (AMR) AF: 0.114 AC: 836 AN: 7310

Ashkenazi Jewish (ASJ) AF: 0.0664 AC: 662 AN: 9976

East Asian (EAS) AF: 0.142 AC: 3182 AN: 22472

South Asian (SAS) AF: 0.0983 AC: 1909 AN: 19414

European-Finnish (FIN) AF: 0.0393 AC: 970 AN: 24668

Middle Eastern (MID) AF: 0.0780 AC: 114 AN: 1462

European-Non Finnish (NFE) AF: 0.0536 AC: 10685 AN: 199206

Other (OTH) AF: 0.0995 AC: 1844 AN: 18528

GnomAD4 genome AF: 0.175 AC: 26565 AN: 152056 Hom.: 4433 Cov.: 33 AF XY: 0.170 AC XY: 12673 AN XY: 74350

African (AFR) AF: 0.441 AC: 18304 AN: 41478

American (AMR) AF: 0.123 AC: 1885 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0637 AC: 221 AN: 3472

East Asian (EAS) AF: 0.188 AC: 966 AN: 5138

South Asian (SAS) AF: 0.133 AC: 644 AN: 4830

European-Finnish (FIN) AF: 0.0391 AC: 415 AN: 10608

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.0556 AC: 3779 AN: 67932

Other (OTH) AF: 0.148 AC: 312 AN: 2112

Alfa AF: 0.131 Hom.: 306

Bravo AF: 0.194

Asia WGS AF: 0.204 AC: 705 AN: 3462

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.82
PhyloP100		0.083
PromoterAI		-0.060	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs2272080; hg19: chr8-22298726;