Variant X-84065009-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014496.5(RPS6KA6):c.2074G>A(p.Asp692Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0608 in 1,203,882 control chromosomes in the GnomAD database, including 2,128 homozygotes. There are 24,300 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.062 ( 229 hom., 1968 hem., cov: 22)

Exomes 𝑓: 0.061 ( 1899 hom. 22332 hem. )

Consequence

RPS6KA6
NM_014496.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.36

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0012203455).

BP6

Variant X-84065009-C-T is Benign according to our data. Variant chrX-84065009-C-T is described in ClinVar as [Benign]. Clinvar id is 1288726.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPS6KA6	NM_014496.5 linkuse as main transcript	c.2074G>A	p.Asp692Asn	missense_variant	21/22	ENST00000262752.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPS6KA6	ENST00000262752.5 linkuse as main transcript	c.2074G>A	p.Asp692Asn	missense_variant	21/22	1	NM_014496.5	P1	Q9UK32-1
RPS6KA6	ENST00000620340.4 linkuse as main transcript	c.2074G>A	p.Asp692Asn	missense_variant	21/22	5			Q9UK32-2

Frequencies

GnomAD3 genomes

AF:

0.0616

AC:

6810

AN:

110615

Hom.:

229

Cov.:

AF XY:

0.0592

AC XY:

1946

AN XY:

32873

show subpopulations

Gnomad AFR

AF:

0.0483

Gnomad AMI

AF:

0.235

Gnomad AMR

AF:

0.0980

Gnomad ASJ

AF:

0.0699

Gnomad EAS

AF:

0.203

Gnomad SAS

AF:

0.0751

Gnomad FIN

AF:

0.0286

Gnomad MID

AF:

0.0921

Gnomad NFE

AF:

0.0527

Gnomad OTH

AF:

0.0698

GnomAD3 exomes

AF:

0.0793

AC:

14518

AN:

183055

Hom.:

597

AF XY:

0.0757

AC XY:

5116

AN XY:

67569

show subpopulations

Gnomad AFR exome

AF:

0.0487

Gnomad AMR exome

AF:

0.121

Gnomad ASJ exome

AF:

0.0701

Gnomad EAS exome

AF:

0.222

Gnomad SAS exome

AF:

0.0876

Gnomad FIN exome

AF:

0.0363

Gnomad NFE exome

AF:

0.0539

Gnomad OTH exome

AF:

0.0733

GnomAD4 exome

AF:

0.0607

AC:

66389

AN:

1093213

Hom.:

1899

Cov.:

AF XY:

0.0622

AC XY:

22332

AN XY:

359001

show subpopulations

Gnomad4 AFR exome

AF:

0.0486

Gnomad4 AMR exome

AF:

0.124

Gnomad4 ASJ exome

AF:

0.0704

Gnomad4 EAS exome

AF:

0.252

Gnomad4 SAS exome

AF:

0.0918

Gnomad4 FIN exome

AF:

0.0349

Gnomad4 NFE exome

AF:

0.0501

Gnomad4 OTH exome

AF:

0.0658

GnomAD4 genome

AF:

0.0617

AC:

6831

AN:

110669

Hom.:

229

Cov.:

AF XY:

0.0598

AC XY:

1968

AN XY:

32937

show subpopulations

Gnomad4 AFR

AF:

0.0488

Gnomad4 AMR

AF:

0.0981

Gnomad4 ASJ

AF:

0.0699

Gnomad4 EAS

AF:

0.203

Gnomad4 SAS

AF:

0.0761

Gnomad4 FIN

AF:

0.0286

Gnomad4 NFE

AF:

0.0527

Gnomad4 OTH

AF:

0.0695

Alfa

AF:

0.0627

Hom.:

3831

Bravo

AF:

0.0710

TwinsUK

AF:

0.0526

AC:

195

ALSPAC

AF:

0.0523

AC:

151

ESP6500AA

AF:

0.0498

AC:

191

ESP6500EA

AF:

0.0528

AC:

355

ExAC

AF:

0.0773

AC:

9383

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	GeneDx	Jan 15, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.91

BayesDel_noAF

Benign

-0.94

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.061

.;T

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.77

T;T

MetaRNN

Benign

0.0012

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

1.3

.;N

REVEL

Benign

0.092

Sift

Benign

0.93

.;T

Sift4G

Benign

0.66

T;T

Polyphen

0.0

.;B

Vest4

0.093

MPC

0.51

ClinPred

0.013

GERP RS

-0.26

Varity_R

0.041

gMVP

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over