PPP3CB p.Gly22Arg

Variant names:

• chr10-73495826-C-G
• NM_021132.4:c.64G>C
• PPP3CB p.Gly22Arg

Your query was ambiguous. Multiple possible variants found:

• chr10-73495826-C-G
• chr10-73495826-C-T
• chr10-73495824-CCC-ACG
• chr10-73495824-CCC-GCG
• chr10-73495824-CCC-TCG
• chr10-73495824-CCC-TCT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021132.4(PPP3CB):​c.64G>C​(p.Gly22Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP3CB NM_021132.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.86
• Publications: 0 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]

PPP3CB-AS1 (HGNC:50750): (PPP3CB antisense RNA 1 (head to head))

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.22386447).

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.64G>C	p.Gly22Arg	missense	Exon 1 of 14	NP_066955.1	P16298-1
	PPP3CB	NM_001142353.3		c.64G>C	p.Gly22Arg	missense	Exon 1 of 14	NP_001135825.1	P16298-4
	PPP3CB	NM_001142354.3		c.64G>C	p.Gly22Arg	missense	Exon 1 of 13	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.64G>C	p.Gly22Arg	missense	Exon 1 of 14	ENSP00000353881.5	P16298-1
	PPP3CB	ENST00000394829.6	TSL:1	c.64G>C	p.Gly22Arg	missense	Exon 1 of 14	ENSP00000378306.2	P16298-4
	PPP3CB	ENST00000394828.6	TSL:1	c.64G>C	p.Gly22Arg	missense	Exon 1 of 13	ENSP00000378305.2	P16298-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000761 AC: 6 AN: 788178 Hom.: 0 Cov.: 28 AF XY: 0.00000989 AC XY: 4 AN XY: 404394

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 15244

American (AMR) AF: 0.00 AC: 0 AN: 28734

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13304

East Asian (EAS) AF: 0.00 AC: 0 AN: 10984

South Asian (SAS) AF: 0.00 AC: 0 AN: 70002

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30044

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3306

European-Non Finnish (NFE) AF: 0.0000102 AC: 6 AN: 586126

Other (OTH) AF: 0.00 AC: 0 AN: 30434

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.46
BayesDel_addAF	Benign	-0.088	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	-0.26
Eigen_PC	Benign	-0.22
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.82	T
M_CAP	Pathogenic	0.65	D
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.14	N
PhyloP100		2.9
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.038
Sift	Uncertain	0.014	D
Sift4G	Benign	0.58	T
PromoterAI		0.030	Neutral
Varity_R		0.20
gMVP		0.37
Mutation Taster		=88/12	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-75255584;