Genetic Variant ENST00000518852.5:c.-451T>G (chr8-22440959-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000518852.5(PPP3CC):c.-451T>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 0.174 in 154,198 control chromosomes in the GnomAD database, including 4,387 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 0.18 ( 4361 hom., cov: 33)

Exomes 𝑓: 0.071 ( 26 hom. )

Consequence

PPP3CC
ENST00000518852.5 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.88

Publications

2 publications found

Variant links:

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)

PPP3CC links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CC	NM_005605.5 link	c.-451T>G		upstream_gene_variant		ENST00000240139.10	NP_005596.2	P48454-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP3CC	ENST00000518852.5 link	c.-451T>G	5_prime_UTR_variant	Exon 1 of 8	2		ENSP00000429379.1	G3V111
PPP3CC	ENST00000240139.10 link	c.-451T>G	upstream_gene_variant		1	NM_005605.5	ENSP00000240139.5	P48454-1
PPP3CC	ENST00000289963.12 link	c.-451T>G	upstream_gene_variant		1		ENSP00000289963.8	P48454-2
PPP3CC	ENST00000397775.7 link	c.-451T>G	upstream_gene_variant		2		ENSP00000380878.3	P48454-3

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26360

AN:

149486

Hom.:

4336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.0100

Gnomad AMR

AF:

0.125

Gnomad ASJ

AF:

0.0642

Gnomad EAS

AF:

0.200

Gnomad SAS

AF:

0.145

Gnomad FIN

AF:

0.0406

Gnomad MID

AF:

0.0962

Gnomad NFE

AF:

0.0562

Gnomad OTH

AF:

0.142

GnomAD4 exome

AF:

0.0709

AC:

325

AN:

4582

Hom.:

Cov.:

AF XY:

0.0699

AC XY:

165

AN XY:

2360

show subpopulations

African (AFR)

AF:

0.459

AC:

AN:

172

American (AMR)

AF:

0.0915

AC:

AN:

142

Ashkenazi Jewish (ASJ)

AF:

0.0680

AC:

AN:

206

East Asian (EAS)

AF:

0.103

AC:

AN:

312

South Asian (SAS)

AF:

0.0769

AC:

AN:

European-Finnish (FIN)

AF:

0.0284

AC:

AN:

176

Middle Eastern (MID)

AF:

0.0833

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0468

AC:

148

AN:

3160

Other (OTH)

AF:

0.0828

AC:

AN:

338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.177

AC:

26445

AN:

149616

Hom.:

4361

Cov.:

AF XY:

0.173

AC XY:

12620

AN XY:

73122

show subpopulations

African (AFR)

AF:

0.442

AC:

18190

AN:

41148

American (AMR)

AF:

0.125

AC:

1889

AN:

15054

Ashkenazi Jewish (ASJ)

AF:

0.0642

AC:

221

AN:

3444

East Asian (EAS)

AF:

0.200

AC:

963

AN:

4808

South Asian (SAS)

AF:

0.143

AC:

644

AN:

4518

European-Finnish (FIN)

AF:

0.0406

AC:

412

AN:

10136

Middle Eastern (MID)

AF:

0.103

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0562

AC:

3777

AN:

67230

Other (OTH)

AF:

0.148

AC:

310

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.514

Heterozygous variant carriers

950

1900

2850

3800

4750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0447

Hom.:

Bravo

AF:

0.194

Asia WGS

AF:

0.203

AC:

701

AN:

3456

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

4.8

(source)

DANN

Benign

0.29

PhyloP100

-1.9

PromoterAI

0.21

Neutral

(source)

Mutation Taster

=300/0

polymorphism (auto)

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over