Genetic Variant NM_020761.3:c.1797C>T (chr17-80883927-C-T) – ACMG Classification: Benign (-15 pts)

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_020761.3(RPTOR):c.1797C>T(p.Ser599Ser) 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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.657

Publications

1 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 -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 17-80883927-C-T is Benign according to our data. Variant chr17-80883927-C-T is described in ClinVar as Benign. ClinVar VariationId is 785586.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.657 with no splicing effect.

BS2

High AC in GnomAd4 at 761 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.1797C>T	p.Ser599Ser	synonymous	Exon 16 of 34	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.1510-7793C>T		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.1797C>T	p.Ser599Ser	synonymous	Exon 16 of 34	ENSP00000307272.3	Q8N122-1
RPTOR	ENST00000575542.5	TSL:1	n.1284C>T		non_coding_transcript_exon	Exon 12 of 30
RPTOR	ENST00000697423.1		c.1851C>T	p.Ser617Ser	synonymous	Exon 16 of 34	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes

AF:

0.00501

AC:

762

AN:

152210

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.00253

AC:

635

AN:

250726

AF XY:

0.00240

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 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.:

Cov.:

AF XY:

0.00138

AC XY:

1000

AN XY:

726868

show subpopulations

African (AFR)

AF:

0.0105

AC:

350

AN:

33480

American (AMR)

AF:

0.00490

AC:

219

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.0126

AC:

330

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86252

European-Finnish (FIN)

AF:

0.0000190

AC:

AN:

52630

Middle Eastern (MID)

AF:

0.0132

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000755

AC:

840

AN:

1111978

Other (OTH)

AF:

0.00335

AC:

202

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

117

235

352

470

587

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

126

168

210

<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:

0.00500

AC:

761

AN:

152328

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

382

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.0112

AC:

465

AN:

41580

American (AMR)

AF:

0.00856

AC:

131

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00109

AC:

AN:

68022

Other (OTH)

AF:

0.0118

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

109

145

181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.00269

Hom.:

Bravo

AF:

0.00596

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.00136

EpiControl

AF:

0.000830

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

5.0

(source)

DANN

Benign

0.58

PhyloP100

-0.66

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=90/10

polymorphism

(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