Genetic Variant RPTOR:c.265+62G>T (chr17-80625855-G-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020761.3(RPTOR):c.265+62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,196,144 control chromosomes in the GnomAD database, including 68,001 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: 𝑓 0.35 ( 9709 hom., cov: 32)

Exomes 𝑓: 0.33 ( 58292 hom. )

Consequence

RPTOR
NM_020761.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0580

Publications

8 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 is higher than 0.05.

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.265+62G>T		intron	N/A	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.265+62G>T		intron	N/A	NP_001156506.1	Q8N122-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.265+62G>T	intron	N/A	ENSP00000307272.3	Q8N122-1
RPTOR	ENST00000570891.5	TSL:1	c.265+62G>T	intron	N/A	ENSP00000460136.1	Q8N122-2
RPTOR	ENST00000697423.1		c.319+62G>T	intron	N/A	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes

AF:

0.352

AC:

53441

AN:

151760

Hom.:

9703

Cov.:

show subpopulations

Gnomad AFR

AF:

0.435

Gnomad AMI

AF:

0.262

Gnomad AMR

AF:

0.302

Gnomad ASJ

AF:

0.294

Gnomad EAS

AF:

0.280

Gnomad SAS

AF:

0.221

Gnomad FIN

AF:

0.248

Gnomad MID

AF:

0.335

Gnomad NFE

AF:

0.348

Gnomad OTH

AF:

0.355

GnomAD4 exome

AF:

0.330

AC:

345045

AN:

1044266

Hom.:

58292

AF XY:

0.327

AC XY:

175512

AN XY:

537522

show subpopulations

African (AFR)

AF:

0.438

AC:

11272

AN:

25746

American (AMR)

AF:

0.233

AC:

10203

AN:

43768

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

6721

AN:

23304

East Asian (EAS)

AF:

0.304

AC:

11543

AN:

37940

South Asian (SAS)

AF:

0.233

AC:

18125

AN:

77690

European-Finnish (FIN)

AF:

0.273

AC:

14332

AN:

52566

Middle Eastern (MID)

AF:

0.330

AC:

1107

AN:

3352

European-Non Finnish (NFE)

AF:

0.350

AC:

256779

AN:

733448

Other (OTH)

AF:

0.322

AC:

14963

AN:

46452

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

11008

22015

33023

44030

55038

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6610

13220

19830

26440

33050

<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:

0.352

AC:

53470

AN:

151878

Hom.:

9709

Cov.:

AF XY:

0.344

AC XY:

25530

AN XY:

74230

show subpopulations

African (AFR)

AF:

0.435

AC:

18007

AN:

41410

American (AMR)

AF:

0.302

AC:

4612

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.294

AC:

1022

AN:

3472

East Asian (EAS)

AF:

0.280

AC:

1434

AN:

5128

South Asian (SAS)

AF:

0.220

AC:

1061

AN:

4812

European-Finnish (FIN)

AF:

0.248

AC:

2616

AN:

10556

Middle Eastern (MID)

AF:

0.350

AC:

103

AN:

294

European-Non Finnish (NFE)

AF:

0.348

AC:

23638

AN:

67916

Other (OTH)

AF:

0.350

AC:

739

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1731

3461

5192

6922

8653

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

500

1000

1500

2000

2500

<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:

0.314

Hom.:

3533

Bravo

AF:

0.357

Asia WGS

AF:

0.218

AC:

761

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.6

(source)

DANN

Benign

0.74

PhyloP100

0.058

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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