10-73495883-C-T

Variant names:

• chr10-73495883-C-T
• rs2057216990
• NM_021132.4:c.7G>A

Variant summary

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

The NM_021132.4(PPP3CB):​c.7G>A​(p.Ala3Thr) 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. A3S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000011 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: PPP3CB NM_021132.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.85

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

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=0.15084395).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PPP3CB	NM_021132.4	c.7G>A	p.Ala3Thr	missense_variant	Exon 1 of 14	ENST00000360663.10	NP_066955.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PPP3CB	ENST00000360663.10	c.7G>A	p.Ala3Thr	missense_variant	Exon 1 of 14	1	NM_021132.4	ENSP00000353881.5

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000107 AC: 1 AN: 935708 Hom.: 0 Cov.: 25 AF XY: 0.00000218 AC XY: 1 AN XY: 458660

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000128

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.25
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.46
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.;.;.
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.34
FATHMM_MKL	Benign	0.031	N
LIST_S2	Benign	0.80	T;T;T;T
M_CAP	Pathogenic	0.68	D
MetaRNN	Benign	0.15	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N;N;N;.
PrimateAI	Pathogenic	0.89	D
PROVEAN	Benign	0.11	N;N;N;N
REVEL	Benign	0.072
Sift	Benign	0.070	T;D;D;D
Sift4G	Benign	0.10	T;T;T;D
Polyphen		0.0080	B;B;.;.
Vest4		0.26
MutPred		0.29		Gain of glycosylation at A3 (P = 0.0014);Gain of glycosylation at A3 (P = 0.0014);Gain of glycosylation at A3 (P = 0.0014);Gain of glycosylation at A3 (P = 0.0014);
MVP		0.16
MPC		0.58
ClinPred		0.34	T
GERP RS		3.9
Varity_R		0.14
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs2057216990; hg19: chr10-75255641;