10-73475068-C-T

Variant names:

• chr10-73475068-C-T
• rs3763679
• NM_021132.4:c.412-38G>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.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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 17 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.312 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.412-38G>A		intron	N/A	NP_066955.1	P16298-1
	PPP3CB	NM_001142353.3		c.412-38G>A		intron	N/A	NP_001135825.1	P16298-4
	PPP3CB	NM_001142354.3		c.412-38G>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.412-38G>A		intron	N/A	ENSP00000353881.5	P16298-1
	PPP3CB	ENST00000394829.6	TSL:1	c.412-38G>A		intron	N/A	ENSP00000378306.2	P16298-4
	PPP3CB	ENST00000394828.6	TSL:1	c.412-38G>A		intron	N/A	ENSP00000378305.2	P16298-3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22868 AN: 151974 Hom.: 2793 Cov.: 32

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

GnomAD2 exomes AF: 0.124 AC: 28570 AN: 230130 AF XY: 0.124

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 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.: 30 AF XY: 0.0911 AC XY: 65379 AN XY: 717334

African (AFR) AF: 0.324 AC: 10571 AN: 32600

American (AMR) AF: 0.0936 AC: 4009 AN: 42850

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 2962 AN: 25674

East Asian (EAS) AF: 0.285 AC: 11149 AN: 39054

South Asian (SAS) AF: 0.220 AC: 18400 AN: 83760

European-Finnish (FIN) AF: 0.0491 AC: 2538 AN: 51736

Middle Eastern (MID) AF: 0.0831 AC: 429 AN: 5164

European-Non Finnish (NFE) AF: 0.0641 AC: 70723 AN: 1103602

Other (OTH) AF: 0.107 AC: 6382 AN: 59524

GnomAD4 genome AF: 0.151 AC: 22945 AN: 152092 Hom.: 2820 Cov.: 32 AF XY: 0.152 AC XY: 11289 AN XY: 74398

African (AFR) AF: 0.317 AC: 13122 AN: 41420

American (AMR) AF: 0.101 AC: 1541 AN: 15278

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

East Asian (EAS) AF: 0.298 AC: 1542 AN: 5166

South Asian (SAS) AF: 0.226 AC: 1090 AN: 4824

European-Finnish (FIN) AF: 0.0448 AC: 475 AN: 10612

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

European-Non Finnish (NFE) AF: 0.0647 AC: 4398 AN: 68010

Other (OTH) AF: 0.123 AC: 258 AN: 2106

Alfa AF: 0.0950 Hom.: 620

Bravo AF: 0.160

Asia WGS AF: 0.262 AC: 908 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.44
PhyloP100		-1.0
Mutation Taster		=100/0	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: rs3763679; hg19: chr10-75234826;