NM_003952.3:c.*186G>T

Variant names:

• chr11-67435355-G-T
• rs10274
• NM_003952.3:c.*186G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003952.3(RPS6KB2):​c.*186G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000314 in 636,530 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RPS6KB2 NM_003952.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 23 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)

CORO1B (HGNC:2253): (coronin 1B) Members of the coronin family, such as CORO1B, are WD repeat-containing actin-binding proteins that regulate cell motility (Cai et al., 2005 [PubMed 16027158]).[supplied by OMIM, Mar 2008]

PTPRCAP (HGNC:9667): (protein tyrosine phosphatase receptor type C associated protein) The protein encoded by this gene was identified as a transmembrane phosphoprotein specifically associated with tyrosine phosphatase PTPRC/CD45, a key regulator of T- and B-lymphocyte activation. The interaction with PTPRC may be required for the stable expression of this protein. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).

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.*186G>T		3_prime_UTR	Exon 15 of 15	NP_003943.2
	CORO1B	NM_020441.3	MANE Select	c.*3021C>A		downstream_gene	N/A	NP_065174.1
	PTPRCAP	NM_005608.3	MANE Select	c.*378C>A		downstream_gene	N/A	NP_005599.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	ENST00000312629.10	TSL:1 MANE Select	c.*186G>T		3_prime_UTR	Exon 15 of 15	ENSP00000308413.5
	RPS6KB2	ENST00000525088.5	TSL:2	n.5482G>T		non_coding_transcript_exon	Exon 8 of 8
	RPS6KB2-AS1	ENST00000535922.1	TSL:3	n.45C>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151990 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000147

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000206 AC: 1 AN: 484540 Hom.: 0 Cov.: 6 AF XY: 0.00000397 AC XY: 1 AN XY: 252192

African (AFR) AF: 0.00 AC: 0 AN: 12914

American (AMR) AF: 0.00 AC: 0 AN: 17104

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13742

East Asian (EAS) AF: 0.00 AC: 0 AN: 30292

South Asian (SAS) AF: 0.00 AC: 0 AN: 45250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2056

European-Non Finnish (NFE) AF: 0.00000326 AC: 1 AN: 306740

Other (OTH) AF: 0.00 AC: 0 AN: 27026

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151990 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74214

African (AFR) AF: 0.00 AC: 0 AN: 41374

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10576

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67988

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 22415

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.96
DANN	Benign	0.54
PhyloP100		-0.70
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs10274; hg19: chr11-67202826;