10-73475068-C-G

Variant names:

• chr10-73475068-C-G
• rs3763679
• NM_021132.4:c.412-38G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021132.4(PPP3CB):​c.412-38G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000692 in 1,444,514 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CB	NM_021132.4	MANE Select	c.412-38G>C		intron	N/A	NP_066955.1
	PPP3CB	NM_001142353.3		c.412-38G>C		intron	N/A	NP_001135825.1
	PPP3CB	NM_001142354.3		c.412-38G>C		intron	N/A	NP_001135826.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PPP3CB	ENST00000360663.10	TSL:1 MANE Select	c.412-38G>C		intron	N/A	ENSP00000353881.5
	PPP3CB	ENST00000394829.6	TSL:1	c.412-38G>C		intron	N/A	ENSP00000378306.2
	PPP3CB	ENST00000394828.6	TSL:1	c.412-38G>C		intron	N/A	ENSP00000378305.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.92e-7 AC: 1 AN: 1444514 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 717628

African (AFR) AF: 0.00 AC: 0 AN: 32656

American (AMR) AF: 0.00 AC: 0 AN: 42896

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25680

East Asian (EAS) AF: 0.00 AC: 0 AN: 39090

South Asian (SAS) AF: 0.00 AC: 0 AN: 83834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51752

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5170

European-Non Finnish (NFE) AF: 9.06e-7 AC: 1 AN: 1103894

Other (OTH) AF: 0.00 AC: 0 AN: 59542

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.2
DANN	Benign	0.69
PhyloP100		-1.0

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;