17-59913236-A-T

Variant names:

• chr17-59913236-A-T
• rs1292033
• NM_003161.4:c.312+432A>T

Variant summary

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

The NM_003161.4(RPS6KB1):​c.312+432A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 152,108 control chromosomes in the GnomAD database, including 2,952 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 0.19 (2952 hom., cov: 32)
• Consequence: RPS6KB1 NM_003161.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• Publications: 9 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=-0.77).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.375 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPS6KB1	NM_003161.4	c.312+432A>T		intron_variant	Intron 3 of 14	ENST00000225577.9	NP_003152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPS6KB1	ENST00000225577.9	c.312+432A>T		intron_variant	Intron 3 of 14	1	NM_003161.4	ENSP00000225577.4

Frequencies

GnomAD3 genomes AF: 0.190 AC: 28909 AN: 151990 Hom.: 2938 Cov.: 32

Gnomad AFR AF: 0.173

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.167

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.389

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.188

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

GnomAD4 genome AF: 0.190 AC: 28963 AN: 152108 Hom.: 2952 Cov.: 32 AF XY: 0.190 AC XY: 14146 AN XY: 74348

African (AFR) AF: 0.174 AC: 7198 AN: 41482

American (AMR) AF: 0.167 AC: 2546 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 465 AN: 3472

East Asian (EAS) AF: 0.389 AC: 2013 AN: 5176

South Asian (SAS) AF: 0.262 AC: 1261 AN: 4820

European-Finnish (FIN) AF: 0.175 AC: 1848 AN: 10572

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13032 AN: 68010

Other (OTH) AF: 0.198 AC: 418 AN: 2114

Alfa AF: 0.0905 Hom.: 140

Bravo AF: 0.186

Asia WGS AF: 0.361 AC: 1255 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		1.3
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: rs1292033; hg19: chr17-57990597;