Genetic Variant RPS6KB1:p.Ala466Val (chr17-59946607-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_003161.4(RPS6KB1):c.1397C>T(p.Ala466Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RPS6KB1
NM_003161.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.94

Publications

0 publications found

Variant links:

Genes affected

RPS6KB1 (HGNC:10436): (ribosomal protein S6 kinase B1) This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation start sites results in isoforms with longer or shorter N-termini which may differ in their subcellular localizations. There are two pseudogenes for this gene on chromosome 17. [provided by RefSeq, Jan 2013]

RPS6KB1 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

RPS6KB1 links:

ENSG00000267318 (HGNC:):

ENSG00000267318 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11126885).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003161.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS6KB1	NM_003161.4	MANE Select	c.1397C>T	p.Ala466Val	missense	Exon 15 of 15	NP_003152.1	P23443-1
RPS6KB1	NM_001272042.2		c.1328C>T	p.Ala443Val	missense	Exon 14 of 14	NP_001258971.1	P23443-5
RPS6KB1	NM_001272060.2		c.1328C>T	p.Ala443Val	missense	Exon 15 of 15	NP_001258989.1	P23443-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPS6KB1	ENST00000225577.9	TSL:1 MANE Select	c.1397C>T	p.Ala466Val	missense	Exon 15 of 15	ENSP00000225577.4	P23443-1
RPS6KB1	ENST00000406116.7	TSL:1	c.1341-980C>T		intron	N/A	ENSP00000384335.3	P23443-4
ENSG00000267318	ENST00000591035.1	TSL:3	c.149+1089C>T		intron	N/A	ENSP00000468280.1	K7ERJ3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.33

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.022

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

M_CAP

Benign

0.013

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.0

PhyloP100

1.9

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.67

REVEL

Benign

0.088

Sift

Benign

0.24

Sift4G

Benign

0.40

Polyphen

0.0

Vest4

0.013

MutPred

0.071

Loss of glycosylation at S462 (P = 0.0944)

MVP

0.67

MPC

1.0

ClinPred

0.48

GERP RS

4.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.087

gMVP

0.48

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over