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GeneBe

17-80883927-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_020761.3(RPTOR):c.1797C>T(p.Ser599=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,613,374 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0014 ( 8 hom. )

Consequence

RPTOR
NM_020761.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.657
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 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=-0.34).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-80883927-C-T is Benign according to our data. Variant chr17-80883927-C-T is described in ClinVar as [Benign]. Clinvar id is 785586.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.657 with no splicing effect.
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 762 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPTORNM_020761.3 linkuse as main transcriptc.1797C>T p.Ser599= synonymous_variant 16/34 ENST00000306801.8
RPTORNM_001163034.2 linkuse as main transcriptc.1510-7793C>T intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPTORENST00000306801.8 linkuse as main transcriptc.1797C>T p.Ser599= synonymous_variant 16/341 NM_020761.3 P1Q8N122-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00501
AC:
762
AN:
152210
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0112
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00857
Gnomad ASJ
AF:
0.0161
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0316
Gnomad NFE
AF:
0.00109
Gnomad OTH
AF:
0.0120
GnomAD3 exomes
AF:
0.00253
AC:
635
AN:
250726
Hom.:
1
AF XY:
0.00240
AC XY:
326
AN XY:
135638
show subpopulations
Gnomad AFR exome
AF:
0.0118
Gnomad AMR exome
AF:
0.00469
Gnomad ASJ exome
AF:
0.0125
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00119
Gnomad OTH exome
AF:
0.00327
GnomAD4 exome
AF:
0.00138
AC:
2019
AN:
1461046
Hom.:
8
Cov.:
32
AF XY:
0.00138
AC XY:
1000
AN XY:
726868
show subpopulations
Gnomad4 AFR exome
AF:
0.0105
Gnomad4 AMR exome
AF:
0.00490
Gnomad4 ASJ exome
AF:
0.0126
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000190
Gnomad4 NFE exome
AF:
0.000755
Gnomad4 OTH exome
AF:
0.00335
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00500
AC:
761
AN:
152328
Hom.:
5
Cov.:
33
AF XY:
0.00513
AC XY:
382
AN XY:
74496
show subpopulations
Gnomad4 AFR
AF:
0.0112
Gnomad4 AMR
AF:
0.00856
Gnomad4 ASJ
AF:
0.0161
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00109
Gnomad4 OTH
AF:
0.0118
Alfa
AF:
0.00269
Hom.:
1
Bravo
AF:
0.00596
Asia WGS
AF:
0.00144
AC:
5
AN:
3478
EpiCase
AF:
0.00136
EpiControl
AF:
0.000830

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 testingInvitaeJul 11, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.34
Cadd
Benign
5.0
Dann
Benign
0.58
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

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: rs61733885; hg19: chr17-78857727; API