Variant X-84104561-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_014496.5(RPS6KA6):c.1552C>T(p.Arg518Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000675 in 1,184,329 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 23 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.000072 ( 0 hom. 22 hem. )

Consequence

RPS6KA6
NM_014496.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.66

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 Likely_benign. Variant got -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.3866013).

BS2

High Hemizygotes in GnomAdExome4 at 22 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA6	NM_014496.5 linkuse as main transcript	c.1552C>T	p.Arg518Trp	missense_variant	17/22	ENST00000262752.5	NP_055311.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KA6	ENST00000262752.5 linkuse as main transcript	c.1552C>T	p.Arg518Trp	missense_variant	17/22	1	NM_014496.5	ENSP00000262752	P1	Q9UK32-1
RPS6KA6	ENST00000620340.4 linkuse as main transcript	c.1552C>T	p.Arg518Trp	missense_variant	17/22	5		ENSP00000483896		Q9UK32-2
RPS6KA6	ENST00000495332.1 linkuse as main transcript	n.284C>T		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes

AF:

0.0000272

AC:

AN:

110195

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32737

show subpopulations

Gnomad AFR

AF:

0.0000657

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000191

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000175

AC:

AN:

171410

Hom.:

AF XY:

0.0000343

AC XY:

AN XY:

58274

show subpopulations

Gnomad AFR exome

AF:

0.0000797

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000603

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000128

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000717

AC:

AN:

1074084

Hom.:

Cov.:

AF XY:

0.0000638

AC XY:

AN XY:

344978

show subpopulations

Gnomad4 AFR exome

AF:

0.0000388

Gnomad4 AMR exome

AF:

0.0000299

Gnomad4 ASJ exome

AF:

0.0000531

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000397

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000798

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

AF:

0.0000272

AC:

AN:

110245

Hom.:

Cov.:

AF XY:

0.0000305

AC XY:

AN XY:

32797

show subpopulations

Gnomad4 AFR

AF:

0.0000655

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000191

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000227

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000346

AC:

ExAC

AF:

0.0000494

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.1552C>T (p.R518W) alteration is located in exon 17 (coding exon 17) of the RPS6KA6 gene. This alteration results from a C to T substitution at nucleotide position 1552, causing the arginine (R) at amino acid position 518 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Uncertain

0.027

BayesDel_noAF

Benign

-0.20

CADD

Uncertain

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.31

.;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Pathogenic

0.42

MetaRNN

Benign

0.39

T;T

MetaSVM

Uncertain

-0.25

MutationAssessor

Benign

1.9

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.33

PROVEAN

Pathogenic

-6.2

.;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.010

.;D

Sift4G

Uncertain

0.019

D;D

Polyphen

1.0

.;D

Vest4

0.20

MVP

0.65

MPC

1.5

ClinPred

0.60

GERP RS

5.3

Varity_R

0.42

gMVP

0.42

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over