11-67428578-G-C

Variant names:

• chr11-67428578-G-C
• rs35363135
• NM_003952.3:c.33G>C

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_003952.3(RPS6KB2):​c.33G>C​(p.Thr11Thr) variant causes a synonymous 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RPS6KB2 NM_003952.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.312
• Publications: 4 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]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP7: Synonymous conserved (PhyloP=-0.312 with no splicing effect.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	NM_003952.3	MANE Select	c.33G>C	p.Thr11Thr	synonymous	Exon 1 of 15	NP_003943.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	ENST00000312629.10	TSL:1 MANE Select	c.33G>C	p.Thr11Thr	synonymous	Exon 1 of 15	ENSP00000308413.5
	RPS6KB2	ENST00000524934.5	TSL:3	c.33G>C	p.Thr11Thr	synonymous	Exon 1 of 5	ENSP00000436811.1
	RPS6KB2	ENST00000524814.5	TSL:3	n.85G>C		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 536

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	9.1
DANN	Benign	0.83
PhyloP100		-0.31
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.8

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

Other links and lift over

dbSNP: rs35363135; hg19: chr11-67196049;