Variant X-84065098-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_014496.5(RPS6KA6):c.1985A>G(p.His662Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00068 in 1,186,477 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 261 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00039 ( 0 hom., 17 hem., cov: 22)

Exomes 𝑓: 0.00071 ( 0 hom. 244 hem. )

Consequence

RPS6KA6
NM_014496.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.61

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 -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.081795245).

BS2

High Hemizygotes in GnomAd4 at 17 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KA6	NM_014496.5 linkuse as main transcript	c.1985A>G	p.His662Arg	missense_variant	21/22	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.1985A>G	p.His662Arg	missense_variant	21/22	1	NM_014496.5	ENSP00000262752	P1	Q9UK32-1
RPS6KA6	ENST00000620340.4 linkuse as main transcript	c.1985A>G	p.His662Arg	missense_variant	21/22	5		ENSP00000483896		Q9UK32-2

Frequencies

GnomAD3 genomes

AF:

0.000389

AC:

AN:

110645

Hom.:

Cov.:

AF XY:

0.000517

AC XY:

AN XY:

32863

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00146

Gnomad AMR

AF:

0.000193

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:

0.000699

Gnomad OTH

AF:

0.00202

GnomAD3 exomes

AF:

0.000325

AC:

AN:

175526

Hom.:

AF XY:

0.000377

AC XY:

AN XY:

60954

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000787

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000345

Gnomad FIN exome

AF:

0.0000632

Gnomad NFE exome

AF:

0.000580

Gnomad OTH exome

AF:

0.000468

GnomAD4 exome

AF:

0.000710

AC:

764

AN:

1075832

Hom.:

Cov.:

AF XY:

0.000710

AC XY:

244

AN XY:

343420

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000236

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000374

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000844

Gnomad4 OTH exome

AF:

0.000619

GnomAD4 genome

AF:

0.000389

AC:

AN:

110645

Hom.:

Cov.:

AF XY:

0.000517

AC XY:

AN XY:

32863

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000193

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000699

Gnomad4 OTH

AF:

0.00202

Alfa

AF:

0.000816

Hom.:

Bravo

AF:

0.000434

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000692

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00119

AC:

ExAC

AF:

0.000288

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

Apr 30, 2024

The c.1985A>G (p.H662R) alteration is located in exon 21 (coding exon 21) of the RPS6KA6 gene. This alteration results from a A to G substitution at nucleotide position 1985, causing the histidine (H) at amino acid position 662 to be replaced by an arginine (R). 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

0.070

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.049

.;T

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.87

D;D

M_CAP

Benign

0.039

MetaRNN

Benign

0.082

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.1

N;N

MutationTaster

Benign

1.0

D;D

PrimateAI

Uncertain

0.69

PROVEAN

Benign

1.2

.;N

REVEL

Uncertain

0.33

Sift

Benign

0.41

.;T

Sift4G

Benign

0.52

T;T

Polyphen

0.0010

.;B

Vest4

0.14

MVP

0.90

MPC

0.63

ClinPred

0.028

GERP RS

3.6

Varity_R

0.16

gMVP

0.68

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