NM_003952.3:c.732T>G

Variant names:

• chr11-67433150-T-G
• NM_003952.3:c.732T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003952.3(RPS6KB2):​c.732T>G​(p.Ser244Arg) 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. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: RPS6KB2 NM_003952.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -2.38
• Publications: 0 publications found

Genes affected

RPS6KB2 (HGNC:10437): (ribosomal protein S6 kinase B2) This gene encodes a member of the RSK (ribosomal S6 kinase) family of serine/threonine kinases. This kinase contains a kinase catalytic domain and phosphorylates the S6 ribosomal protein and eukaryotic translation initiation factor 4B (eIF4B). Phosphorylation of S6 leads to an increase in protein synthesis and cell proliferation. [provided by RefSeq, Jan 2015]

RPS6KB2-AS1 (HGNC:53744): (RPS6KB2 antisense RNA 1)

ACMG classification

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=0.19812164).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003952.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	NM_003952.3	MANE Select	c.732T>G	p.Ser244Arg	missense	Exon 9 of 15	NP_003943.2	Q9UBS0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	ENST00000312629.10	TSL:1 MANE Select	c.732T>G	p.Ser244Arg	missense	Exon 9 of 15	ENSP00000308413.5	Q9UBS0-1
	RPS6KB2	ENST00000942409.1		c.732T>G	p.Ser244Arg	missense	Exon 9 of 15	ENSP00000612468.1
	RPS6KB2	ENST00000875118.1		c.738T>G	p.Ser246Arg	missense	Exon 9 of 15	ENSP00000545177.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.30	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-0.99
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.032	D
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.68	N
PhyloP100		-2.4
PrimateAI	Uncertain	0.72	T
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.22
Sift	Benign	0.49	T
Sift4G	Benign	0.56	T
Polyphen		0.0090	B
Vest4		0.48
MutPred		0.50		Gain of MoRF binding (P = 0.0184)
MVP		0.34
MPC		0.14
ClinPred		0.16	T
GERP RS		-1.5
Varity_R		0.36
gMVP		0.64
Mutation Taster		=84/16	polymorphism

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

Other links and lift over

hg19: chr11-67200621;