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GeneBe

17-80837970-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2

The NM_020761.3(RPTOR):c.1185G>A(p.Thr395=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00447 in 1,611,670 control chromosomes in the GnomAD database, including 103 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 38 hom., cov: 33)
Exomes 𝑓: 0.0035 ( 65 hom. )

Consequence

RPTOR
NM_020761.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.707
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 -15 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=-0.53).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 17-80837970-G-A is Benign according to our data. Variant chr17-80837970-G-A is described in ClinVar as [Benign]. Clinvar id is 778753.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=-0.707 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0141 (2143/152286) while in subpopulation AFR AF= 0.04 (1664/41556). AF 95% confidence interval is 0.0384. There are 38 homozygotes in gnomad4. There are 990 alleles in male gnomad4 subpopulation. Median coverage is 33. 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 2132 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
RPTORNM_020761.3 linkuse as main transcriptc.1185G>A p.Thr395= synonymous_variant 10/34 ENST00000306801.8
RPTORNM_001163034.2 linkuse as main transcriptc.1185G>A p.Thr395= synonymous_variant 10/30

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
RPTORENST00000306801.8 linkuse as main transcriptc.1185G>A p.Thr395= synonymous_variant 10/341 NM_020761.3 P1Q8N122-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0140
AC:
2132
AN:
152168
Hom.:
36
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0399
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0160
Gnomad ASJ
AF:
0.00691
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0411
Gnomad NFE
AF:
0.00243
Gnomad OTH
AF:
0.0153
GnomAD3 exomes
AF:
0.00563
AC:
1391
AN:
246888
Hom.:
17
AF XY:
0.00474
AC XY:
632
AN XY:
133302
show subpopulations
Gnomad AFR exome
AF:
0.0422
Gnomad AMR exome
AF:
0.00905
Gnomad ASJ exome
AF:
0.00718
Gnomad EAS exome
AF:
0.0000545
Gnomad SAS exome
AF:
0.0000336
Gnomad FIN exome
AF:
0.0000471
Gnomad NFE exome
AF:
0.00257
Gnomad OTH exome
AF:
0.0104
GnomAD4 exome
AF:
0.00347
AC:
5057
AN:
1459384
Hom.:
65
Cov.:
31
AF XY:
0.00328
AC XY:
2381
AN XY:
725700
show subpopulations
Gnomad4 AFR exome
AF:
0.0430
Gnomad4 AMR exome
AF:
0.0103
Gnomad4 ASJ exome
AF:
0.00781
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000701
Gnomad4 FIN exome
AF:
0.0000376
Gnomad4 NFE exome
AF:
0.00217
Gnomad4 OTH exome
AF:
0.00759
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0141
AC:
2143
AN:
152286
Hom.:
38
Cov.:
33
AF XY:
0.0133
AC XY:
990
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.0400
Gnomad4 AMR
AF:
0.0160
Gnomad4 ASJ
AF:
0.00691
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00243
Gnomad4 OTH
AF:
0.0151
Alfa
AF:
0.00664
Hom.:
5
Bravo
AF:
0.0168
Asia WGS
AF:
0.00462
AC:
16
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 testingInvitaeDec 31, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.53
Cadd
Benign
1.3
Dann
Benign
0.77

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: rs113149562; hg19: chr17-78811770; COSMIC: COSV100157812; API