Genetic Variant PPP3CB:c.412-38G>A (chr10-73475068-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_021132.4(PPP3CB):c.412-38G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.094 in 1,596,056 control chromosomes in the GnomAD database, including 11,524 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 0.15 ( 2820 hom., cov: 32)

Exomes 𝑓: 0.088 ( 8704 hom. )

Consequence

PPP3CB
NM_021132.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.00

Variant links:

Genes affected

PPP3CB (HGNC:9315): (protein phosphatase 3 catalytic subunit beta) Enables several functions, including calmodulin binding activity; calmodulin-dependent protein phosphatase activity; and protein phosphatase 2B binding activity. Involved in calcineurin-NFAT signaling cascade; positive regulation of transcription by RNA polymerase II; and protein dephosphorylation. Located in cytoplasm. Part of calcineurin complex. Implicated in aortic valve stenosis. Biomarker of focal segmental glomerulosclerosis and schizophrenia. [provided by Alliance of Genome Resources, Apr 2022]

PPP3CB links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CB	NM_021132.4 link	c.412-38G>A		intron_variant	Intron 3 of 13	ENST00000360663.10	NP_066955.1	P16298-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
PPP3CB	ENST00000360663.10 link	c.412-38G>A	intron_variant	Intron 3 of 13	1	NM_021132.4	ENSP00000353881.5	P16298-1
PPP3CB	ENST00000394829.6 link	c.412-38G>A	intron_variant	Intron 3 of 13	1		ENSP00000378306.2	P16298-4
PPP3CB	ENST00000394828.6 link	c.412-38G>A	intron_variant	Intron 3 of 12	1		ENSP00000378305.2	P16298-3
PPP3CB	ENST00000342558.3 link	c.412-38G>A	intron_variant	Intron 3 of 11	5		ENSP00000343147.3	Q5F2F8

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22868

AN:

151974

Hom.:

2793

Cov.:

show subpopulations

Gnomad AFR

AF:

0.316

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.101

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.298

Gnomad SAS

AF:

0.227

Gnomad FIN

AF:

0.0448

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.0646

Gnomad OTH

AF:

0.120

GnomAD3 exomes

AF:

0.124

AC:

28570

AN:

230130

Hom.:

2754

AF XY:

0.124

AC XY:

15560

AN XY:

125466

show subpopulations

Gnomad AFR exome

AF:

0.322

Gnomad AMR exome

AF:

0.0935

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.301

Gnomad SAS exome

AF:

0.226

Gnomad FIN exome

AF:

0.0482

Gnomad NFE exome

AF:

0.0659

Gnomad OTH exome

AF:

0.0911

GnomAD4 exome

AF:

0.0881

AC:

127163

AN:

1443964

Hom.:

8704

Cov.:

AF XY:

0.0911

AC XY:

65379

AN XY:

717334

show subpopulations

Gnomad4 AFR exome

AF:

0.324

Gnomad4 AMR exome

AF:

0.0936

Gnomad4 ASJ exome

AF:

0.115

Gnomad4 EAS exome

AF:

0.285

Gnomad4 SAS exome

AF:

0.220

Gnomad4 FIN exome

AF:

0.0491

Gnomad4 NFE exome

AF:

0.0641

Gnomad4 OTH exome

AF:

0.107

GnomAD4 genome

AF:

0.151

AC:

22945

AN:

152092

Hom.:

2820

Cov.:

AF XY:

0.152

AC XY:

11289

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.317

Gnomad4 AMR

AF:

0.101

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.298

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.0448

Gnomad4 NFE

AF:

0.0647

Gnomad4 OTH

AF:

0.123

Alfa

AF:

0.0967

Hom.:

592

Bravo

AF:

0.160

Asia WGS

AF:

0.262

AC:

908

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

4.0

DANN

Benign

0.44

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over