17-59936844-A-G

Variant names:

• chr17-59936844-A-G
• rs180522
• NM_003161.4:c.1119+303A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003161.4(RPS6KB1):​c.1119+303A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.143 in 152,104 control chromosomes in the GnomAD database, including 1,699 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 0.14 (1699 hom., cov: 32)
• Consequence: RPS6KB1 NM_003161.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 5 publications found

Genes affected

RPS6KB1 (HGNC:10436): (ribosomal protein S6 kinase B1) This gene encodes a member of the ribosomal S6 kinase family of serine/threonine kinases. The encoded protein responds to mTOR (mammalian target of rapamycin) signaling to promote protein synthesis, cell growth, and cell proliferation. Activity of this gene has been associated with human cancer. Alternatively spliced transcript variants have been observed. The use of alternative translation start sites results in isoforms with longer or shorter N-termini which may differ in their subcellular localizations. There are two pseudogenes for this gene on chromosome 17. [provided by RefSeq, Jan 2013]

RPS6KB1 Gene-Disease associations (from GenCC):

• hypertrophic cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.161 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003161.4. 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
	RPS6KB1	NM_003161.4	MANE Select	c.1119+303A>G		intron	N/A	NP_003152.1
	RPS6KB1	NM_001272042.2		c.1050+303A>G		intron	N/A	NP_001258971.1
	RPS6KB1	NM_001272060.2		c.1050+303A>G		intron	N/A	NP_001258989.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPS6KB1	ENST00000225577.9	TSL:1 MANE Select	c.1119+303A>G		intron	N/A	ENSP00000225577.4
	RPS6KB1	ENST00000406116.7	TSL:1	c.1119+303A>G		intron	N/A	ENSP00000384335.3
	RPS6KB1	ENST00000443572.6	TSL:2	c.1050+303A>G		intron	N/A	ENSP00000441993.1

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21734 AN: 151986 Hom.: 1701 Cov.: 32

Gnomad AFR AF: 0.105

Gnomad AMI AF: 0.264

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.170

Gnomad EAS AF: 0.0704

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.158

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.164

Gnomad OTH AF: 0.155

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.143 AC: 21726 AN: 152104 Hom.: 1699 Cov.: 32 AF XY: 0.143 AC XY: 10634 AN XY: 74348

African (AFR) AF: 0.104 AC: 4337 AN: 41508

American (AMR) AF: 0.162 AC: 2474 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.170 AC: 590 AN: 3470

East Asian (EAS) AF: 0.0703 AC: 364 AN: 5176

South Asian (SAS) AF: 0.110 AC: 528 AN: 4810

European-Finnish (FIN) AF: 0.158 AC: 1665 AN: 10562

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11152 AN: 67988

Other (OTH) AF: 0.152 AC: 321 AN: 2106

Alfa AF: 0.152 Hom.: 247

Bravo AF: 0.142

Asia WGS AF: 0.0830 AC: 289 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.56
DANN	Benign	0.66
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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: rs180522; hg19: chr17-58014205;