Variant 11-64361956-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000334205.9(RPS6KA4):c.860C>T(p.Ala287Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000719 in 1,610,484 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00042 ( 4 hom. )

Consequence

RPS6KA4
ENST00000334205.9 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.30

Variant links:

Genes affected

RPS6KA4 (HGNC:10433): (ribosomal protein S6 kinase A4) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains 2 non-identical kinase catalytic domains and phosphorylates various substrates, including CREB1 and ATF1. The encoded protein can also phosphorylate histone H3 to regulate certain inflammatory genes. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

RPS6KA4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00985986).

BP6

Variant 11-64361956-C-T is Benign according to our data. Variant chr11-64361956-C-T is described in ClinVar as [Benign]. Clinvar id is 787911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 543 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA4	NM_003942.3 linkuse as main transcript	c.860C>T	p.Ala287Val	missense_variant	8/17	ENST00000334205.9	NP_003933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA4	ENST00000334205.9 linkuse as main transcript	c.860C>T	p.Ala287Val	missense_variant	8/17	1	NM_003942.3	ENSP00000333896	P1	O75676-1

Frequencies

GnomAD3 genomes

AF:

0.00356

AC:

541

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0126

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00101

AC:

249

AN:

247400

Hom.:

AF XY:

0.000730

AC XY:

AN XY:

134218

show subpopulations

Gnomad AFR exome

AF:

0.0144

Gnomad AMR exome

AF:

0.000269

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000446

Gnomad OTH exome

AF:

0.000498

GnomAD4 exome

AF:

0.000422

AC:

615

AN:

1458236

Hom.:

Cov.:

AF XY:

0.000357

AC XY:

259

AN XY:

725650

show subpopulations

Gnomad4 AFR exome

AF:

0.0156

Gnomad4 AMR exome

AF:

0.000436

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.000797

GnomAD4 genome

AF:

0.00357

AC:

543

AN:

152248

Hom.:

Cov.:

AF XY:

0.00344

AC XY:

256

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0126

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000882

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.000966

Hom.:

Bravo

AF:

0.00458

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0134

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00116

AC:

141

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 21, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.43

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

.;T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

0.00079

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.95

D;D;D

MetaRNN

Benign

0.0099

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

.;L;.

MutationTaster

Benign

0.99

D;D;D

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-2.6

D;D;D

REVEL

Benign

0.11

Sift

Uncertain

0.010

D;D;D

Sift4G

Benign

0.11

T;T;T

Polyphen

0.061

B;B;.

Vest4

0.32

MVP

0.47

MPC

0.47

ClinPred

0.030

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.57

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over