Menu
GeneBe

17-59893319-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003161.4(RPS6KB1):c.135G>A(p.Glu45=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00138 in 1,607,990 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0076 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00073 ( 12 hom. )

Consequence

RPS6KB1
NM_003161.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.30
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.48).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-59893319-G-A is Benign according to our data. Variant chr17-59893319-G-A is described in ClinVar as [Benign]. Clinvar id is 781310.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00756 (1152/152328) while in subpopulation AFR AF= 0.0262 (1088/41562). AF 95% confidence interval is 0.0249. There are 11 homozygotes in gnomad4. There are 532 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 1153 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPS6KB1NM_003161.4 linkuse as main transcriptc.135G>A p.Glu45= synonymous_variant 1/15 ENST00000225577.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPS6KB1ENST00000225577.9 linkuse as main transcriptc.135G>A p.Glu45= synonymous_variant 1/151 NM_003161.4 A1P23443-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00758
AC:
1153
AN:
152210
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0263
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00321
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00621
GnomAD3 exomes
AF:
0.00187
AC:
435
AN:
232282
Hom.:
6
AF XY:
0.00136
AC XY:
172
AN XY:
126768
show subpopulations
Gnomad AFR exome
AF:
0.0276
Gnomad AMR exome
AF:
0.00124
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000482
Gnomad OTH exome
AF:
0.000882
GnomAD4 exome
AF:
0.000728
AC:
1059
AN:
1455662
Hom.:
12
Cov.:
31
AF XY:
0.000619
AC XY:
448
AN XY:
723622
show subpopulations
Gnomad4 AFR exome
AF:
0.0266
Gnomad4 AMR exome
AF:
0.00139
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000117
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000721
Gnomad4 OTH exome
AF:
0.00161
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00756
AC:
1152
AN:
152328
Hom.:
11
Cov.:
32
AF XY:
0.00714
AC XY:
532
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.0262
Gnomad4 AMR
AF:
0.00320
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00615
Alfa
AF:
0.00373
Hom.:
4
Bravo
AF:
0.00862
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeApr 09, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.48
Cadd
Benign
14
Dann
Benign
0.96
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.8

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs56376112; hg19: chr17-57970680; COSMIC: COSV56679900; COSMIC: COSV56679900; API