rs2289759

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_020761.3(RPTOR):ā€‹c.1518A>Gā€‹(p.Gln506=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,612,836 control chromosomes in the GnomAD database, including 54,709 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: š‘“ 0.23 ( 4096 hom., cov: 32)
Exomes š‘“: 0.26 ( 50613 hom. )

Consequence

RPTOR
NM_020761.3 synonymous

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.857
Variant links:
Genes affected
RPTOR (HGNC:30287): (regulatory associated protein of MTOR complex 1) This gene encodes a component of a signaling pathway that regulates cell growth in response to nutrient and insulin levels. The encoded protein forms a stoichiometric complex with the mTOR kinase, and also associates with eukaryotic initiation factor 4E-binding protein-1 and ribosomal protein S6 kinase. The protein positively regulates the downstream effector ribosomal protein S6 kinase, and negatively regulates the mTOR kinase. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.6).
BP7
Synonymous conserved (PhyloP=-0.857 with no splicing effect.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RPTORNM_020761.3 linkuse as main transcriptc.1518A>G p.Gln506= synonymous_variant 14/34 ENST00000306801.8 NP_065812.1
RPTORNM_001163034.2 linkuse as main transcriptc.1510-11297A>G intron_variant NP_001156506.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RPTORENST00000306801.8 linkuse as main transcriptc.1518A>G p.Gln506= synonymous_variant 14/341 NM_020761.3 ENSP00000307272 P1Q8N122-1

Frequencies

GnomAD3 genomes
AF:
0.226
AC:
34373
AN:
152032
Hom.:
4092
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.143
Gnomad AMI
AF:
0.207
Gnomad AMR
AF:
0.253
Gnomad ASJ
AF:
0.247
Gnomad EAS
AF:
0.371
Gnomad SAS
AF:
0.283
Gnomad FIN
AF:
0.206
Gnomad MID
AF:
0.168
Gnomad NFE
AF:
0.258
Gnomad OTH
AF:
0.241
GnomAD3 exomes
AF:
0.258
AC:
64765
AN:
251220
Hom.:
8787
AF XY:
0.259
AC XY:
35189
AN XY:
135844
show subpopulations
Gnomad AFR exome
AF:
0.138
Gnomad AMR exome
AF:
0.269
Gnomad ASJ exome
AF:
0.254
Gnomad EAS exome
AF:
0.383
Gnomad SAS exome
AF:
0.264
Gnomad FIN exome
AF:
0.208
Gnomad NFE exome
AF:
0.260
Gnomad OTH exome
AF:
0.257
GnomAD4 exome
AF:
0.260
AC:
380484
AN:
1460686
Hom.:
50613
Cov.:
33
AF XY:
0.261
AC XY:
189433
AN XY:
726686
show subpopulations
Gnomad4 AFR exome
AF:
0.136
Gnomad4 AMR exome
AF:
0.265
Gnomad4 ASJ exome
AF:
0.253
Gnomad4 EAS exome
AF:
0.367
Gnomad4 SAS exome
AF:
0.266
Gnomad4 FIN exome
AF:
0.210
Gnomad4 NFE exome
AF:
0.263
Gnomad4 OTH exome
AF:
0.259
GnomAD4 genome
AF:
0.226
AC:
34392
AN:
152150
Hom.:
4096
Cov.:
32
AF XY:
0.226
AC XY:
16845
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.143
Gnomad4 AMR
AF:
0.253
Gnomad4 ASJ
AF:
0.247
Gnomad4 EAS
AF:
0.371
Gnomad4 SAS
AF:
0.284
Gnomad4 FIN
AF:
0.206
Gnomad4 NFE
AF:
0.258
Gnomad4 OTH
AF:
0.241
Alfa
AF:
0.253
Hom.:
6399
Bravo
AF:
0.225
Asia WGS
AF:
0.310
AC:
1077
AN:
3478
EpiCase
AF:
0.264
EpiControl
AF:
0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.60
CADD
Benign
0.28
DANN
Benign
0.56

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: rs2289759; hg19: chr17-78854223; COSMIC: COSV60803658; API