Genetic Variant NM_020761.3:c.-261G>A (chr17-80545369-G-A) – 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.-261G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 352,010 control chromosomes in the GnomAD database, including 6,889 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 0.16 ( 2352 hom., cov: 32)

Exomes 𝑓: 0.20 ( 4537 hom. )

Consequence

RPTOR
NM_020761.3 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.780

Publications

18 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:

ENSG00000289764 (HGNC:):

ENSG00000289764 links:

Genome browser will be placed here

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=-0.78).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3 link	c.-261G>A		5_prime_UTR_variant	Exon 1 of 34	ENST00000306801.8	NP_065812.1	Q8N122-1Q6DKI0
RPTOR	NM_001163034.2 link	c.-261G>A		5_prime_UTR_variant	Exon 1 of 30		NP_001156506.1	Q8N122-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8 link	c.-261G>A		5_prime_UTR_variant	Exon 1 of 34	1	NM_020761.3	ENSP00000307272.3		Q8N122-1
ENSG00000289764	ENST00000699258.2 link	c.*235G>A		downstream_gene_variant				ENSP00000514239.1		A0A8V8TPC4

Frequencies

GnomAD3 genomes

AF:

0.165

AC:

25053

AN:

152068

Hom.:

2351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0630

Gnomad AMI

AF:

0.202

Gnomad AMR

AF:

0.174

Gnomad ASJ

AF:

0.185

Gnomad EAS

AF:

0.275

Gnomad SAS

AF:

0.191

Gnomad FIN

AF:

0.181

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.210

Gnomad OTH

AF:

0.179

GnomAD4 exome

AF:

0.204

AC:

40675

AN:

199824

Hom.:

4537

Cov.:

AF XY:

0.203

AC XY:

20608

AN XY:

101618

show subpopulations

African (AFR)

AF:

0.0662

AC:

422

AN:

6376

American (AMR)

AF:

0.155

AC:

1042

AN:

6704

Ashkenazi Jewish (ASJ)

AF:

0.181

AC:

1424

AN:

7868

East Asian (EAS)

AF:

0.320

AC:

5655

AN:

17684

South Asian (SAS)

AF:

0.178

AC:

1572

AN:

8844

European-Finnish (FIN)

AF:

0.195

AC:

2401

AN:

12306

Middle Eastern (MID)

AF:

0.175

AC:

178

AN:

1020

European-Non Finnish (NFE)

AF:

0.204

AC:

25576

AN:

125576

Other (OTH)

AF:

0.179

AC:

2405

AN:

13446

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1724

3447

5171

6894

8618

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

154

308

462

616

770

<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:

0.165

AC:

25062

AN:

152186

Hom.:

2352

Cov.:

AF XY:

0.165

AC XY:

12285

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0634

AC:

2634

AN:

41564

American (AMR)

AF:

0.174

AC:

2656

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.185

AC:

642

AN:

3472

East Asian (EAS)

AF:

0.275

AC:

1423

AN:

5170

South Asian (SAS)

AF:

0.191

AC:

919

AN:

4822

European-Finnish (FIN)

AF:

0.181

AC:

1914

AN:

10582

Middle Eastern (MID)

AF:

0.201

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.210

AC:

14259

AN:

67962

Other (OTH)

AF:

0.176

AC:

372

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1053

2105

3158

4210

5263

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<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:

0.192

Hom.:

8136

Bravo

AF:

0.159

Asia WGS

AF:

0.176

AC:

615

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

0.78

PromoterAI

-0.038

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=300/0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over