Variant 11-67433341-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000312629.10(RPS6KB2):c.800C>T(p.Pro267Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0463 in 1,611,958 control chromosomes in the GnomAD database, including 1,980 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.036 ( 103 hom., cov: 33)

Exomes 𝑓: 0.047 ( 1877 hom. )

Consequence

RPS6KB2
ENST00000312629.10 missense, splice_region

Scores

Splicing: ADA: 0.006512

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.34

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:

RPS6KB2-AS1 (HGNC:53744): (RPS6KB2 antisense RNA 1)

RPS6KB2-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01272276).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0518 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.800C>T	p.Pro267Leu	missense_variant, splice_region_variant	10/15	ENST00000312629.10	NP_003943.2
RPS6KB2	XM_047427395.1 linkuse as main transcript	c.778C>T	p.Arg260Cys	missense_variant, splice_region_variant	10/11		XP_047283351.1
RPS6KB2	XM_006718656.4 linkuse as main transcript	c.200C>T	p.Pro67Leu	missense_variant, splice_region_variant	6/11		XP_006718719.1
RPS6KB2	XM_047427396.1 linkuse as main transcript	c.709C>T	p.Arg237Cys	missense_variant, splice_region_variant	9/10		XP_047283352.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10 linkuse as main transcript	c.800C>T	p.Pro267Leu	missense_variant, splice_region_variant	10/15	1	NM_003952.3	ENSP00000308413	P1	Q9UBS0-1
RPS6KB2-AS1	ENST00000535922.1 linkuse as main transcript	n.343+1716G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.0364

AC:

5536

AN:

152142

Hom.:

103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00961

Gnomad AMI

AF:

0.0471

Gnomad AMR

AF:

0.0236

Gnomad ASJ

AF:

0.0544

Gnomad EAS

AF:

0.0566

Gnomad SAS

AF:

0.0249

Gnomad FIN

AF:

0.0403

Gnomad MID

AF:

0.0316

Gnomad NFE

AF:

0.0532

Gnomad OTH

AF:

0.0349

GnomAD3 exomes

AF:

0.0421

AC:

10486

AN:

249268

Hom.:

253

AF XY:

0.0430

AC XY:

5820

AN XY:

135300

show subpopulations

Gnomad AFR exome

AF:

0.00866

Gnomad AMR exome

AF:

0.0202

Gnomad ASJ exome

AF:

0.0534

Gnomad EAS exome

AF:

0.0613

Gnomad SAS exome

AF:

0.0247

Gnomad FIN exome

AF:

0.0408

Gnomad NFE exome

AF:

0.0538

Gnomad OTH exome

AF:

0.0499

GnomAD4 exome

AF:

0.0474

AC:

69181

AN:

1459698

Hom.:

1877

Cov.:

AF XY:

0.0469

AC XY:

34094

AN XY:

726364

show subpopulations

Gnomad4 AFR exome

AF:

0.00726

Gnomad4 AMR exome

AF:

0.0202

Gnomad4 ASJ exome

AF:

0.0524

Gnomad4 EAS exome

AF:

0.0524

Gnomad4 SAS exome

AF:

0.0260

Gnomad4 FIN exome

AF:

0.0450

Gnomad4 NFE exome

AF:

0.0515

Gnomad4 OTH exome

AF:

0.0423

GnomAD4 genome

AF:

0.0363

AC:

5533

AN:

152260

Hom.:

103

Cov.:

AF XY:

0.0344

AC XY:

2560

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00960

Gnomad4 AMR

AF:

0.0236

Gnomad4 ASJ

AF:

0.0544

Gnomad4 EAS

AF:

0.0563

Gnomad4 SAS

AF:

0.0251

Gnomad4 FIN

AF:

0.0403

Gnomad4 NFE

AF:

0.0532

Gnomad4 OTH

AF:

0.0336

Alfa

AF:

0.0472

Hom.:

175

Bravo

AF:

0.0361

TwinsUK

AF:

0.0529

AC:

196

ALSPAC

AF:

0.0529

AC:

204

ESP6500AA

AF:

0.0117

AC:

ESP6500EA

AF:

0.0537

AC:

443

ExAC

AF:

0.0432

AC:

5218

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

EpiCase

AF:

0.0526

EpiControl

AF:

0.0524

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.68

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Benign

0.95

DEOGEN2

Benign

0.40

Eigen

Benign

0.0082

Eigen_PC

Benign

0.018

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.80

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.91

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.74

PROVEAN

Pathogenic

-8.9

REVEL

Benign

0.27

Sift

Benign

0.63

Sift4G

Benign

0.33

Polyphen

1.0

Vest4

0.32

MPC

0.53

ClinPred

0.083

GERP RS

4.4

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.1

Varity_R

0.34

gMVP

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0065

dbscSNV1_RF

Benign

0.028

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over