10-73438267-C-T

Position:

• chr10-73438267-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_021132.4(PPP3CB):​c.1550G>A​(p.Gly517Glu) variant causes a missense change. 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.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PPP3CB NM_021132.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.88

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25589764).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP3CB	NM_021132.4	c.1550G>A	p.Gly517Glu	missense_variant	14/14	ENST00000360663.10	NP_066955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PPP3CB	ENST00000360663.10	c.1550G>A	p.Gly517Glu	missense_variant	14/14	1	NM_021132.4	ENSP00000353881.5
PPP3CB	ENST00000394829.6	c.1553G>A	p.Gly518Glu	missense_variant	14/14	1		ENSP00000378306.2
PPP3CB	ENST00000394828.6	c.1523G>A	p.Gly508Glu	missense_variant	13/13	1		ENSP00000378305.2
PPP3CB	ENST00000430762.6	c.539G>A	p.Gly180Glu	missense_variant	7/7	3		ENSP00000398022.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.1553G>A (p.G518E) alteration is located in exon 14 (coding exon 14) of the PPP3CB gene. This alteration results from a G to A substitution at nucleotide position 1553, causing the glycine (G) at amino acid position 518 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.023	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	26
DANN	Uncertain	0.98
DEOGEN2	Benign	0.17	T;.;.;T
Eigen	Benign	0.11
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.26	T;T;T;T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	0.69	N;.;.;.
PrimateAI	Pathogenic	0.80	D
PROVEAN	Benign	-1.1	N;N;N;.
REVEL	Benign	0.23
Sift	Benign	0.23	T;T;T;.
Sift4G	Benign	0.26	T;T;T;T
Polyphen		0.0020	B;.;.;.
Vest4		0.42
MutPred		0.17		Gain of solvent accessibility (P = 0.005);.;.;.;
MVP		0.29
MPC		0.83
ClinPred		0.69	D
GERP RS		5.6
Varity_R		0.13
gMVP		0.76

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr10-75198025;