chr11-67428766-T-G

Variant names:

• chr11-67428766-T-G
• rs1476792
• NM_003952.3:c.78+143T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_003952.3(RPS6KB2):​c.78+143T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000128 in 779,374 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000013 (0 hom.)
• Consequence: RPS6KB2 NM_003952.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.275
• 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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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.78+143T>G		intron	N/A	NP_003943.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB2	ENST00000312629.10	TSL:1 MANE Select	c.78+143T>G		intron	N/A	ENSP00000308413.5
	RPS6KB2	ENST00000525088.5	TSL:2	n.262T>G		non_coding_transcript_exon	Exon 1 of 8
	RPS6KB2	ENST00000524934.5	TSL:3	c.78+143T>G		intron	N/A	ENSP00000436811.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000128 AC: 1 AN: 779374 Hom.: 0 Cov.: 10 AF XY: 0.00000249 AC XY: 1 AN XY: 401468

African (AFR) AF: 0.00 AC: 0 AN: 19540

American (AMR) AF: 0.00 AC: 0 AN: 32478

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18540

East Asian (EAS) AF: 0.00 AC: 0 AN: 33022

South Asian (SAS) AF: 0.0000165 AC: 1 AN: 60436

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42654

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4390

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 530898

Other (OTH) AF: 0.00 AC: 0 AN: 37416

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	5.8
DANN	Benign	0.69
PhyloP100		-0.28
PromoterAI		0.050	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.95		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.95		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1476792; hg19: chr11-67196237;