Variant X-84064396-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014496.5(RPS6KA6):c.2119A>G(p.Met707Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000352 in 1,193,229 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 127 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., 9 hem., cov: 22)

Exomes 𝑓: 0.00035 ( 0 hom. 118 hem. )

Consequence

RPS6KA6
NM_014496.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.46

Variant links:

Genes affected

RPS6KA6 (HGNC:10435): (ribosomal protein S6 kinase A6) This gene encodes a member of ribosomal S6 kinase family, serine-threonine protein kinases which are regulated by growth factors. The encoded protein may be distinct from other members of this family, however, as studies suggest it is not growth factor dependent and may not participate in the same signaling pathways. [provided by RefSeq, Jan 2010]

RPS6KA6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.008620024).

BP6

Variant X-84064396-T-C is Benign according to our data. Variant chrX-84064396-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2660996.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Hemizygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA6	NM_014496.5 linkuse as main transcript	c.2119A>G	p.Met707Val	missense_variant	22/22	ENST00000262752.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA6	ENST00000262752.5 linkuse as main transcript	c.2119A>G	p.Met707Val	missense_variant	22/22	1	NM_014496.5	P1	Q9UK32-1
RPS6KA6	ENST00000620340.4 linkuse as main transcript	c.2119A>G	p.Met707Val	missense_variant	22/22	5			Q9UK32-2

Frequencies

GnomAD3 genomes

AF:

0.000385

AC:

AN:

109163

Hom.:

Cov.:

AF XY:

0.000286

AC XY:

AN XY:

31497

show subpopulations

Gnomad AFR

AF:

0.000937

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000198

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:

0.000228

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000195

AC:

AN:

164493

Hom.:

AF XY:

0.0000950

AC XY:

AN XY:

52645

show subpopulations

Gnomad AFR exome

AF:

0.000963

Gnomad AMR exome

AF:

0.000167

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000667

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000202

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000348

AC:

377

AN:

1084024

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

118

AN XY:

351504

show subpopulations

Gnomad4 AFR exome

AF:

0.00104

Gnomad4 AMR exome

AF:

0.000214

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000593

Gnomad4 FIN exome

AF:

0.0000249

Gnomad4 NFE exome

AF:

0.000386

Gnomad4 OTH exome

AF:

0.000330

GnomAD4 genome

AF:

0.000394

AC:

AN:

109205

Hom.:

Cov.:

AF XY:

0.000285

AC XY:

AN XY:

31549

show subpopulations

Gnomad4 AFR

AF:

0.000969

Gnomad4 AMR

AF:

0.000198

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000228

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000338

Hom.:

Bravo

AF:

0.000555

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.000522

AC:

ESP6500EA

AF:

0.000446

AC:

ExAC

AF:

0.000214

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

RPS6KA6: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.61

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.74

DEOGEN2

Benign

0.10

.;T

FATHMM_MKL

Benign

0.67

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.014

MetaRNN

Benign

0.0086

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.060

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.26

PROVEAN

Benign

-1.4

.;N

REVEL

Benign

0.090

Sift

Benign

0.74

.;T

Sift4G

Benign

0.75

T;T

Polyphen

0.0

.;B

Vest4

0.024

MVP

0.30

MPC

0.52

ClinPred

0.013

GERP RS

3.0

Varity_R

0.24

gMVP

0.32

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