Variant 17-80837970-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

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

Clinical Significance

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

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]

RPTOR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.707 with no splicing effect.

BS1

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

High AC in GnomAd4 at 2143 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3 linkuse as main transcript	c.1185G>A	p.Thr395=	synonymous_variant	10/34	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2 linkuse as main transcript	c.1185G>A	p.Thr395=	synonymous_variant	10/30		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8 linkuse as main transcript	c.1185G>A	p.Thr395=	synonymous_variant	10/34	1	NM_020761.3	ENSP00000307272	P1	Q8N122-1

Frequencies

GnomAD3 genomes

AF:

0.0140

AC:

2132

AN:

152168

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.0141

AC:

2143

AN:

152286

Hom.:

Cov.:

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.:

Bravo

AF:

0.0168

Asia WGS

AF:

0.00462

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over