Variant 11-67433348-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 NM_003952.3(RPS6KB2):c.807C>T(p.Phe269Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,611,276 control chromosomes in the GnomAD database, including 138,985 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 0.38 ( 11229 hom., cov: 32)

Exomes 𝑓: 0.41 ( 127756 hom. )

Consequence

RPS6KB2
NM_003952.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0700

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 (HGNC:):

RPS6KB2 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 (BayesDel_noAF=-0.66).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.436 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KB2	NM_003952.3 linkuse as main transcript	c.807C>T	p.Phe269Phe	synonymous_variant	10/15	ENST00000312629.10	NP_003943.2	Q9UBS0-1
RPS6KB2	XM_047427395.1 linkuse as main transcript	c.785C>T	p.Ser262Leu	missense_variant	10/11		XP_047283351.1
RPS6KB2	XM_047427396.1 linkuse as main transcript	c.716C>T	p.Ser239Leu	missense_variant	9/10		XP_047283352.1
RPS6KB2	XM_006718656.4 linkuse as main transcript	c.207C>T	p.Phe69Phe	synonymous_variant	6/11		XP_006718719.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB2	ENST00000312629.10 linkuse as main transcript	c.807C>T	p.Phe269Phe	synonymous_variant	10/15	1	NM_003952.3	ENSP00000308413.5		Q9UBS0-1

Frequencies

GnomAD3 genomes

AF:

0.380

AC:

57737

AN:

151968

Hom.:

11215

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.364

Gnomad AMR

AF:

0.445

Gnomad ASJ

AF:

0.317

Gnomad EAS

AF:

0.292

Gnomad SAS

AF:

0.247

Gnomad FIN

AF:

0.372

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.425

Gnomad OTH

AF:

0.371

GnomAD3 exomes

AF:

0.394

AC:

98315

AN:

249280

Hom.:

20670

AF XY:

0.385

AC XY:

52112

AN XY:

135294

show subpopulations

Gnomad AFR exome

AF:

0.321

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.313

Gnomad EAS exome

AF:

0.284

Gnomad SAS exome

AF:

0.258

Gnomad FIN exome

AF:

0.369

Gnomad NFE exome

AF:

0.419

Gnomad OTH exome

AF:

0.394

GnomAD4 exome

AF:

0.413

AC:

603277

AN:

1459192

Hom.:

127756

Cov.:

AF XY:

0.407

AC XY:

295830

AN XY:

726030

show subpopulations

Gnomad4 AFR exome

AF:

0.325

Gnomad4 AMR exome

AF:

0.551

Gnomad4 ASJ exome

AF:

0.311

Gnomad4 EAS exome

AF:

0.307

Gnomad4 SAS exome

AF:

0.264

Gnomad4 FIN exome

AF:

0.374

Gnomad4 NFE exome

AF:

0.432

Gnomad4 OTH exome

AF:

0.396

GnomAD4 genome

AF:

0.380

AC:

57787

AN:

152084

Hom.:

11229

Cov.:

AF XY:

0.374

AC XY:

27824

AN XY:

74338

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.445

Gnomad4 ASJ

AF:

0.317

Gnomad4 EAS

AF:

0.292

Gnomad4 SAS

AF:

0.246

Gnomad4 FIN

AF:

0.372

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.369

Alfa

AF:

0.411

Hom.:

8050

Bravo

AF:

0.391

Asia WGS

AF:

0.325

AC:

1132

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.3

DANN

Benign

0.66

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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