Genetic Variant RPTOR:p.Arg532Arg (chr17-80883428-C-A) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_020761.3(RPTOR):c.1594C>A(p.Arg532Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,614,142 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 15 hom. )

Consequence

RPTOR
NM_020761.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.57

Publications

0 publications found

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]

RPTOR links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 17-80883428-C-A is Benign according to our data. Variant chr17-80883428-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2648430.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.57 with no splicing effect.

BS2

High AC in GnomAd4 at 302 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020761.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.1594C>A	p.Arg532Arg	synonymous	Exon 15 of 34	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.1510-8292C>A		intron	N/A	NP_001156506.1	Q8N122-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.1594C>A	p.Arg532Arg	synonymous	Exon 15 of 34	ENSP00000307272.3	Q8N122-1
RPTOR	ENST00000575542.5	TSL:1	n.1081C>A		non_coding_transcript_exon	Exon 11 of 30
RPTOR	ENST00000697423.1		c.1648C>A	p.Arg550Arg	synonymous	Exon 15 of 34	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes

AF:

0.00199

AC:

303

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0204

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000957

GnomAD2 exomes

AF:

0.00245

AC:

616

AN:

251472

AF XY:

0.00244

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000376

Gnomad ASJ exome

AF:

0.0000992

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0203

Gnomad NFE exome

AF:

0.00133

Gnomad OTH exome

AF:

0.00163

GnomAD4 exome

AF:

0.00130

AC:

1904

AN:

1461830

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

894

AN XY:

727224

show subpopulations

African (AFR)

AF:

0.000119

AC:

AN:

33480

American (AMR)

AF:

0.000291

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.000191

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0184

AC:

984

AN:

53376

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000745

AC:

828

AN:

1111994

Other (OTH)

AF:

0.00116

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

102

204

307

409

511

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00198

AC:

302

AN:

152312

Hom.:

Cov.:

AF XY:

0.00273

AC XY:

203

AN XY:

74466

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41570

American (AMR)

AF:

0.0000653

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0204

AC:

216

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

68030

Other (OTH)

AF:

0.000947

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

104

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000930

Hom.:

Bravo

AF:

0.000416

EpiCase

AF:

0.000327

EpiControl

AF:

0.000771

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

4.4

(source)

DANN

Benign

0.55

PhyloP100

1.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

Splicevardb

2.0

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over