Variant rs2229712 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002953.4(RPS6KA1):c.1004A>C(p.Lys335Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.217 in 1,613,156 control chromosomes in the GnomAD database, including 40,223 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. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.18 ( 3001 hom., cov: 32)

Exomes 𝑓: 0.22 ( 37222 hom. )

Consequence

RPS6KA1
NM_002953.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.21

Variant links:

Genes affected

RPS6KA1 (HGNC:10430): (ribosomal protein S6 kinase A1) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 nonidentical kinase catalytic domains and phosphorylates various substrates, including members of the mitogen-activated kinase (MAPK) signalling pathway. The activity of this protein has been implicated in controlling cell growth and differentiation. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

RPS6KA1 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=0.0016505122).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA1	NM_002953.4 linkuse as main transcript	c.1004A>C	p.Lys335Thr	missense_variant	13/22	ENST00000374168.7	NP_002944.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA1	ENST00000374168.7 linkuse as main transcript	c.1004A>C	p.Lys335Thr	missense_variant	13/22	1	NM_002953.4	ENSP00000363283	P1	Q15418-1

Frequencies

GnomAD3 genomes

AF:

0.177

AC:

26886

AN:

152080

Hom.:

2999

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0404

Gnomad AMI

AF:

0.273

Gnomad AMR

AF:

0.257

Gnomad ASJ

AF:

0.308

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.245

Gnomad FIN

AF:

0.198

Gnomad MID

AF:

0.168

Gnomad NFE

AF:

0.225

Gnomad OTH

AF:

0.192

GnomAD3 exomes

AF:

0.219

AC:

55162

AN:

251326

Hom.:

6654

AF XY:

0.225

AC XY:

30536

AN XY:

135840

show subpopulations

Gnomad AFR exome

AF:

0.0405

Gnomad AMR exome

AF:

0.288

Gnomad ASJ exome

AF:

0.292

Gnomad EAS exome

AF:

0.168

Gnomad SAS exome

AF:

0.253

Gnomad FIN exome

AF:

0.202

Gnomad NFE exome

AF:

0.220

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.221

AC:

322785

AN:

1460958

Hom.:

37222

Cov.:

AF XY:

0.223

AC XY:

162396

AN XY:

726802

show subpopulations

Gnomad4 AFR exome

AF:

0.0340

Gnomad4 AMR exome

AF:

0.289

Gnomad4 ASJ exome

AF:

0.293

Gnomad4 EAS exome

AF:

0.201

Gnomad4 SAS exome

AF:

0.258

Gnomad4 FIN exome

AF:

0.198

Gnomad4 NFE exome

AF:

0.221

Gnomad4 OTH exome

AF:

0.214

GnomAD4 genome

AF:

0.177

AC:

26889

AN:

152198

Hom.:

3001

Cov.:

AF XY:

0.180

AC XY:

13399

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.0403

Gnomad4 AMR

AF:

0.257

Gnomad4 ASJ

AF:

0.308

Gnomad4 EAS

AF:

0.179

Gnomad4 SAS

AF:

0.245

Gnomad4 FIN

AF:

0.198

Gnomad4 NFE

AF:

0.225

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.220

Hom.:

6904

Bravo

AF:

0.174

TwinsUK

AF:

0.226

AC:

837

ALSPAC

AF:

0.216

AC:

834

ESP6500AA

AF:

0.0474

AC:

209

ESP6500EA

AF:

0.238

AC:

2051

ExAC

AF:

0.212

AC:

25691

Asia WGS

AF:

0.196

AC:

682

AN:

3478

EpiCase

AF:

0.227

EpiControl

AF:

0.221

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

T;.;.;.;.

Eigen

Benign

0.12

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Pathogenic

0.98

MetaRNN

Benign

0.0017

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.84

L;.;.;.;.

MutationTaster

Benign

1.2e-7

P;P;P;P;P;P

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-2.1

N;N;N;N;N

REVEL

Benign

0.17

Sift

Benign

0.31

T;T;T;T;T

Sift4G

Benign

0.33

T;T;T;T;T

Polyphen

0.29

B;.;.;.;B

Vest4

0.26

MPC

0.74

ClinPred

0.039

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.66

gMVP

0.66

Splicing

Name

Calibrated prediction

Score

Prediction

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