17-59946963-A-G

Position:

• chr17-59946963-A-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_003161.4(RPS6KB1):​c.*175A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,437,914 control chromosomes in the GnomAD database, including 30,046 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 0.15 (2287 hom., cov: 31)
  • Exomes 𝑓: 0.20 (27759 hom.)
• Consequence: RPS6KB1 NM_003161.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.290

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]

ENSG00000267318 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPS6KB1	NM_003161.4	c.*175A>G		3_prime_UTR_variant	15/15	ENST00000225577.9	NP_003152.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPS6KB1	ENST00000225577.9	c.*175A>G		3_prime_UTR_variant	15/15	1	NM_003161.4	ENSP00000225577.4
ENSG00000267318	ENST00000591035.1	c.149+1445A>G		intron_variant		3		ENSP00000468280.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22957 AN: 151968 Hom.: 2279 Cov.: 31

Gnomad AFR AF: 0.0377

Gnomad AMI AF: 0.164

Gnomad AMR AF: 0.152

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.391

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.175

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.191

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.199 AC: 255325 AN: 1285828 Hom.: 27759 Cov.: 31 AF XY: 0.201 AC XY: 125602 AN XY: 624280

Gnomad4 AFR exome AF: 0.0268

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.143

Gnomad4 EAS exome AF: 0.423

Gnomad4 SAS exome AF: 0.270

Gnomad4 FIN exome AF: 0.178

Gnomad4 NFE exome AF: 0.195

Gnomad4 OTH exome AF: 0.187

GnomAD4 genome AF: 0.151 AC: 22973 AN: 152086 Hom.: 2287 Cov.: 31 AF XY: 0.153 AC XY: 11353 AN XY: 74324

Gnomad4 AFR AF: 0.0376

Gnomad4 AMR AF: 0.151

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.390

Gnomad4 SAS AF: 0.263

Gnomad4 FIN AF: 0.175

Gnomad4 NFE AF: 0.191

Gnomad4 OTH AF: 0.162

Alfa AF: 0.184 Hom.: 5102

Bravo AF: 0.141

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	16
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs1051424; hg19: chr17-58024324;