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GeneBe

17-80883478-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020761.3(RPTOR):c.1644G>A(p.Thr548=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00882 in 1,613,948 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0061 ( 5 hom., cov: 33)
Exomes 𝑓: 0.0091 ( 76 hom. )

Consequence

RPTOR
NM_020761.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.17
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 -11 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=-0.82).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-80883478-G-A is Benign according to our data. Variant chr17-80883478-G-A is described in ClinVar as [Benign]. Clinvar id is 770450.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=-1.17 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 932 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPTORNM_020761.3 linkuse as main transcriptc.1644G>A p.Thr548= synonymous_variant 15/34 ENST00000306801.8
RPTORNM_001163034.2 linkuse as main transcriptc.1510-8242G>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPTORENST00000306801.8 linkuse as main transcriptc.1644G>A p.Thr548= synonymous_variant 15/341 NM_020761.3 P1Q8N122-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00613
AC:
932
AN:
152134
Hom.:
5
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00193
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00602
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00166
Gnomad FIN
AF:
0.00113
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0105
Gnomad OTH
AF:
0.0100
GnomAD3 exomes
AF:
0.00570
AC:
1432
AN:
251414
Hom.:
10
AF XY:
0.00574
AC XY:
780
AN XY:
135898
show subpopulations
Gnomad AFR exome
AF:
0.00191
Gnomad AMR exome
AF:
0.00434
Gnomad ASJ exome
AF:
0.00129
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00170
Gnomad FIN exome
AF:
0.00116
Gnomad NFE exome
AF:
0.00987
Gnomad OTH exome
AF:
0.00636
GnomAD4 exome
AF:
0.00910
AC:
13295
AN:
1461696
Hom.:
76
Cov.:
32
AF XY:
0.00883
AC XY:
6422
AN XY:
727150
show subpopulations
Gnomad4 AFR exome
AF:
0.00143
Gnomad4 AMR exome
AF:
0.00463
Gnomad4 ASJ exome
AF:
0.00149
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00155
Gnomad4 FIN exome
AF:
0.00173
Gnomad4 NFE exome
AF:
0.0109
Gnomad4 OTH exome
AF:
0.00931
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00612
AC:
932
AN:
152252
Hom.:
5
Cov.:
33
AF XY:
0.00568
AC XY:
423
AN XY:
74422
show subpopulations
Gnomad4 AFR
AF:
0.00192
Gnomad4 AMR
AF:
0.00601
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00166
Gnomad4 FIN
AF:
0.00113
Gnomad4 NFE
AF:
0.0105
Gnomad4 OTH
AF:
0.00994
Alfa
AF:
0.00764
Hom.:
4
Bravo
AF:
0.00601
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0110
EpiControl
AF:
0.0106

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
-0.82
Cadd
Benign
0.14
Dann
Benign
0.50
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs34848699; hg19: chr17-78857278; COSMIC: COSV100155807; API