Variant rs35363135 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_003952.3(RPS6KB2):c.33G>A(p.Thr11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,611,052 control chromosomes in the GnomAD database, including 6,533 homozygotes. 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: 𝑓 0.12 ( 3526 hom., cov: 32)

Exomes 𝑓: 0.013 ( 3007 hom. )

Consequence

RPS6KB2
NM_003952.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.312

Variant links:

Genes affected

RPS6KB2 (HGNC:10437): (ribosomal protein S6 kinase B2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains a kinase catalytic domain and phosphorylates the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation. [provided by RefSeq, Jan 2015]

RPS6KB2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.24).

BP7

Synonymous conserved (PhyloP=-0.312 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RPS6KB2	NM_003952.3 linkuse as main transcript	c.33G>A	p.Thr11=	synonymous_variant	1/15	ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1 linkuse as main transcript	c.33G>A	p.Thr11=	synonymous_variant	1/11		XP_047283351.1
RPS6KB2	XM_047427396.1 linkuse as main transcript	c.33G>A	p.Thr11=	synonymous_variant	1/10		XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10 linkuse as main transcript	c.33G>A	p.Thr11=	synonymous_variant	1/15	1	NM_003952.3	ENSP00000308413	P1	Q9UBS0-1

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18041

AN:

152136

Hom.:

3525

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0516

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.00245

Gnomad OTH

AF:

0.0870

GnomAD3 exomes

AF:

0.0291

AC:

6829

AN:

234914

Hom.:

1187

AF XY:

0.0223

AC XY:

2883

AN XY:

129258

show subpopulations

Gnomad AFR exome

AF:

0.407

Gnomad AMR exome

AF:

0.0215

Gnomad ASJ exome

AF:

0.00774

Gnomad EAS exome

AF:

0.0000566

Gnomad SAS exome

AF:

0.000560

Gnomad FIN exome

AF:

0.000146

Gnomad NFE exome

AF:

0.00189

Gnomad OTH exome

AF:

0.0168

GnomAD4 exome

AF:

0.0125

AC:

18299

AN:

1458798

Hom.:

3007

Cov.:

AF XY:

0.0108

AC XY:

7859

AN XY:

725668

show subpopulations

Gnomad4 AFR exome

AF:

0.410

Gnomad4 AMR exome

AF:

0.0249

Gnomad4 ASJ exome

AF:

0.00771

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000801

Gnomad4 FIN exome

AF:

0.000135

Gnomad4 NFE exome

AF:

0.00137

Gnomad4 OTH exome

AF:

0.0264

GnomAD4 genome

AF:

0.119

AC:

18062

AN:

152254

Hom.:

3526

Cov.:

AF XY:

0.113

AC XY:

8434

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.0514

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00124

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00246

Gnomad4 OTH

AF:

0.0861

Alfa

AF:

0.0112

Hom.:

105

Bravo

AF:

0.133

Asia WGS

AF:

0.0180

AC:

AN:

3478

EpiCase

AF:

0.00213

EpiControl

AF:

0.00238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Benign

0.94

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over