dbSNP rs35363135: RPS6KB2:p.Thr11Thr (chr11-67428578-G-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_003952.3(RPS6KB2):c.33G>A(p.Thr11Thr) 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

Publications

4 publications found

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 was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RPS6KB2	NM_003952.3 link	c.33G>A	p.Thr11Thr	synonymous_variant	Exon 1 of 15	ENST00000312629.10	NP_003943.2	Q9UBS0-1
RPS6KB2	XM_047427395.1 link	c.33G>A	p.Thr11Thr	synonymous_variant	Exon 1 of 11		XP_047283351.1
RPS6KB2	XM_047427396.1 link	c.33G>A	p.Thr11Thr	synonymous_variant	Exon 1 of 10		XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10 link	c.33G>A	p.Thr11Thr	synonymous_variant	Exon 1 of 15	1	NM_003952.3	ENSP00000308413.5		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

GnomAD2 exomes

AF:

0.0291

AC:

6829

AN:

234914

AF XY:

0.0223

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 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

African (AFR)

AF:

0.410

AC:

13691

AN:

33408

American (AMR)

AF:

0.0249

AC:

1111

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.00771

AC:

201

AN:

26060

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39664

South Asian (SAS)

AF:

0.000801

AC:

AN:

86162

European-Finnish (FIN)

AF:

0.000135

AC:

AN:

51940

Middle Eastern (MID)

AF:

0.0185

AC:

104

AN:

5634

European-Non Finnish (NFE)

AF:

0.00137

AC:

1525

AN:

1111170

Other (OTH)

AF:

0.0264

AC:

1589

AN:

60168

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

618

1236

1854

2472

3090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

390

780

1170

1560

1950

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.119

AC:

18062

AN:

152254

Hom.:

3526

Cov.:

AF XY:

0.113

AC XY:

8434

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.407

AC:

16879

AN:

41512

American (AMR)

AF:

0.0514

AC:

787

AN:

15308

Ashkenazi Jewish (ASJ)

AF:

0.00605

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00124

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.0680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00246

AC:

167

AN:

68022

Other (OTH)

AF:

0.0861

AC:

182

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

564

1128

1691

2255

2819

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

148

296

444

592

740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0298

Hom.:

536

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

(source)

DANN

Benign

0.94

PhyloP100

-0.31

PromoterAI

-0.022

Neutral

(source)

RBP_binding_hub_radar

0.97

RBP_regulation_power_radar

3.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over