11-67428578-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Moderate BP7 BA1

The NM_003952.3(RPS6KB2):​c.33G>A​(p.Thr11Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0226 in 1,611,052 control chromosomes in the GnomAD database, including 6,533 homozygotes. 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: 𝑓 0.12 (3526 hom., cov: 32)
  • Exomes 𝑓: 0.013 (3007 hom.)
• 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: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BP7: Synonymous conserved (PhyloP=-0.312 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.401 is higher than 0.05.

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>A	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>A	p.Thr11Thr	synonymous	Exon 1 of 15	ENSP00000308413.5
	RPS6KB2	ENST00000524934.5	TSL:3	c.33G>A	p.Thr11Thr	synonymous	Exon 1 of 5	ENSP00000436811.1
	RPS6KB2	ENST00000524814.5	TSL:3	n.85G>A		non_coding_transcript_exon	Exon 1 of 7

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18041 AN: 152136 Hom.: 3525 Cov.: 32

Gnomad AFR AF: 0.407

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0516

Gnomad ASJ AF: 0.00605

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.0870

GnomAD2 exomes AF: 0.0291 AC: 6829 AN: 234914 AF XY: 0.0223

Gnomad AFR exome AF: 0.407

Gnomad AMR exome AF: 0.0215

Gnomad ASJ exome AF: 0.00774

Gnomad EAS exome AF: 0.0000566

Gnomad FIN exome AF: 0.000146

Gnomad NFE exome AF: 0.00189

Gnomad OTH exome AF: 0.0168

GnomAD4 exome AF: 0.0125 AC: 18299 AN: 1458798 Hom.: 3007 Cov.: 31 AF XY: 0.0108 AC XY: 7859 AN XY: 725668

African (AFR) AF: 0.410 AC: 13691 AN: 33408

American (AMR) AF: 0.0249 AC: 1111 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.00771 AC: 201 AN: 26060

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39664

South Asian (SAS) AF: 0.000801 AC: 69 AN: 86162

European-Finnish (FIN) AF: 0.000135 AC: 7 AN: 51940

Middle Eastern (MID) AF: 0.0185 AC: 104 AN: 5634

European-Non Finnish (NFE) AF: 0.00137 AC: 1525 AN: 1111170

Other (OTH) AF: 0.0264 AC: 1589 AN: 60168

GnomAD4 genome AF: 0.119 AC: 18062 AN: 152254 Hom.: 3526 Cov.: 32 AF XY: 0.113 AC XY: 8434 AN XY: 74450

African (AFR) AF: 0.407 AC: 16879 AN: 41512

American (AMR) AF: 0.0514 AC: 787 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00605 AC: 21 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00124 AC: 6 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.0680 AC: 20 AN: 294

European-Non Finnish (NFE) AF: 0.00246 AC: 167 AN: 68022

Other (OTH) AF: 0.0861 AC: 182 AN: 2114

Alfa AF: 0.0298 Hom.: 536

Bravo AF: 0.133

Asia WGS AF: 0.0180 AC: 64 AN: 3478

EpiCase AF: 0.00213

EpiControl AF: 0.00238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	10
DANN	Benign	0.94
PhyloP100		-0.31
PromoterAI		-0.022	Neutral
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		3.8
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;