10-73480219-C-T

Variant names:

• chr10-73480219-C-T
• rs11000671
• NM_021132.4:c.86-702G>A

Variant summary

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

The NM_021132.4(PPP3CB):​c.86-702G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 151,286 control chromosomes in the GnomAD database, including 2,693 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 (2693 hom., cov: 32)
• Consequence: PPP3CB NM_021132.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.99
• Publications: 10 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021132.4. 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
	PPP3CB	NM_021132.4	MANE Select	c.86-702G>A		intron	N/A	NP_066955.1	P16298-1
	PPP3CB	NM_001142353.3		c.86-702G>A		intron	N/A	NP_001135825.1	P16298-4
	PPP3CB	NM_001142354.3		c.86-702G>A		intron	N/A	NP_001135826.1	P16298-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CB	ENST00000360663.10	TSL:1 MANE Select	c.86-702G>A		intron	N/A	ENSP00000353881.5	P16298-1
	PPP3CB	ENST00000394829.6	TSL:1	c.86-702G>A		intron	N/A	ENSP00000378306.2	P16298-4
	PPP3CB	ENST00000394828.6	TSL:1	c.86-702G>A		intron	N/A	ENSP00000378305.2	P16298-3

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22455 AN: 151172 Hom.: 2668 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.100

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.299

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.0450

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0648

Gnomad OTH AF: 0.119

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.149 AC: 22528 AN: 151286 Hom.: 2693 Cov.: 32 AF XY: 0.150 AC XY: 11082 AN XY: 73970

African (AFR) AF: 0.311 AC: 12714 AN: 40904

American (AMR) AF: 0.100 AC: 1528 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 395 AN: 3470

East Asian (EAS) AF: 0.300 AC: 1551 AN: 5176

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4812

European-Finnish (FIN) AF: 0.0450 AC: 474 AN: 10532

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0648 AC: 4399 AN: 67854

Other (OTH) AF: 0.121 AC: 255 AN: 2104

Alfa AF: 0.0910 Hom.: 1121

Bravo AF: 0.157

Asia WGS AF: 0.261 AC: 907 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.11
DANN	Benign	0.72
PhyloP100		-3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11000671; hg19: chr10-75239977;