Variant 2-55558840-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001122964.3(PPP4R3B):c.2389C>T(p.Pro797Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000018 in 1,613,536 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

PPP4R3B
NM_001122964.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.81

Variant links:

Genes affected

PPP4R3B (HGNC:29267): (protein phosphatase 4 regulatory subunit 3B) Predicted to act upstream of or within positive regulation of gluconeogenesis and protein dephosphorylation. Located in centrosome and nuclear speck. [provided by Alliance of Genome Resources, Apr 2022]

PPP4R3B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.08729163).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP4R3B	NM_001122964.3 linkuse as main transcript	c.2389C>T	p.Pro797Ser	missense_variant	16/17	ENST00000616407.2	NP_001116436.3	Q5MIZ7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
PPP4R3B	ENST00000616407.2 linkuse as main transcript	c.2389C>T	p.Pro797Ser	missense_variant	16/17	1	NM_001122964.3	ENSP00000483228.1	Q5MIZ7-1
PPP4R3B	ENST00000616288.4 linkuse as main transcript	c.2293C>T	p.Pro765Ser	missense_variant	15/16	1		ENSP00000484116.1	Q5MIZ7-2
PPP4R3B	ENST00000611717.4 linkuse as main transcript	c.2134C>T	p.Pro712Ser	missense_variant	14/15	1		ENSP00000478677.1	Q5MIZ7-3

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152136

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

251220

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135770

show subpopulations

Gnomad AFR exome

AF:

0.000431

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461400

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727024

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

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:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000158

AC:

AN:

152136

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.000555

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000965

Hom.:

Bravo

AF:

0.000189

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 26, 2024

The c.2389C>T (p.P797S) alteration is located in exon 16 (coding exon 16) of the PPP4R3B gene. This alteration results from a C to T substitution at nucleotide position 2389, causing the proline (P) at amino acid position 797 to be replaced by a serine (S). 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

0.063

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.013

.;.;T

Eigen

Benign

0.079

Eigen_PC

Uncertain

0.25

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.85

T;T;T

M_CAP

Benign

0.0043

MetaRNN

Benign

0.087

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

.;.;L

PrimateAI

Benign

0.39

Sift4G

Benign

0.46

T;T;T

Polyphen

0.28

B;B;P

Vest4

0.33

MVP

0.043

ClinPred

0.069

GERP RS

5.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.30

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over