Variant chr2-55558777-T-G 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.2452A>C(p.Lys818Gln) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000689 in 1,450,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

PPP4R3B
NM_001122964.3 missense, splice_region

Scores

Splicing: ADA: 0.8445

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.15

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:

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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=0.14004606).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PPP4R3B	NM_001122964.3 linkuse as main transcript	c.2452A>C	p.Lys818Gln	missense_variant, splice_region_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.2452A>C	p.Lys818Gln	missense_variant, splice_region_variant	16/17	1	NM_001122964.3	ENSP00000483228.1	Q5MIZ7-1
PPP4R3B	ENST00000616288.4 linkuse as main transcript	c.2356A>C	p.Lys786Gln	missense_variant, splice_region_variant	15/16	1		ENSP00000484116.1	Q5MIZ7-2
PPP4R3B	ENST00000611717.4 linkuse as main transcript	c.2197A>C	p.Lys733Gln	missense_variant, splice_region_variant	14/15	1		ENSP00000478677.1	Q5MIZ7-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247298

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133668

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000336

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.89e-7

AC:

AN:

1450590

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

720958

show subpopulations

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Mar 14, 2023

The c.2452A>C (p.K818Q) alteration is located in exon 16 (coding exon 16) of the PPP4R3B gene. This alteration results from a A to C substitution at nucleotide position 2452, causing the lysine (K) at amino acid position 818 to be replaced by a glutamine (Q). 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

0.16

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.014

.;.;T

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.88

D;D;D

M_CAP

Benign

0.0047

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.87

MutationAssessor

Benign

1.3

.;.;L

PrimateAI

Uncertain

0.67

Sift4G

Benign

0.22

T;T;T

Polyphen

0.81

P;P;B

Vest4

0.55

MutPred

0.22

.;.;Loss of ubiquitination at K818 (P = 0.0063);

MVP

0.043

ClinPred

0.42

GERP RS

5.9

Varity_R

0.16

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.84

dbscSNV1_RF

Benign

0.65

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