17-80885016-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_020761.3(RPTOR):c.1851C>T(p.Cys617=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00357 in 1,609,020 control chromosomes in the GnomAD database, including 154 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (92 hom., cov: 34)
  • Exomes 𝑓: 0.0021 (62 hom.)
• Consequence: RPTOR NM_020761.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.128

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.49).
• BP6: Variant 17-80885016-C-T is Benign according to our data. Variant chr17-80885016-C-T is described in ClinVar as [Benign]. Clinvar id is 777272.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.128 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.058 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.1851C>T	p.Cys617=	synonymous_variant	17/34	ENST00000306801.8
RPTOR	NM_001163034.2	c.1510-6704C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.1851C>T	p.Cys617=	synonymous_variant	17/34	1	NM_020761.3	P1

Frequencies

GnomAD3 genomes AF: 0.0174 AC: 2654 AN: 152240 Hom.: 90 Cov.: 34

Gnomad AFR AF: 0.0599

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00719

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000514

Gnomad OTH AF: 0.00955

GnomAD3 exomes AF: 0.00478 AC: 1146 AN: 239546 Hom.: 28 AF XY: 0.00346 AC XY: 448 AN XY: 129460

Gnomad AFR exome AF: 0.0601

Gnomad AMR exome AF: 0.00418

Gnomad ASJ exome AF: 0.000721

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000104

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000527

Gnomad OTH exome AF: 0.00466

GnomAD4 exome AF: 0.00212 AC: 3082 AN: 1456662 Hom.: 62 Cov.: 31 AF XY: 0.00185 AC XY: 1341 AN XY: 724010

Gnomad4 AFR exome AF: 0.0595

Gnomad4 AMR exome AF: 0.00484

Gnomad4 ASJ exome AF: 0.000579

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000189

Gnomad4 FIN exome AF: 0.0000191

Gnomad4 NFE exome AF: 0.000459

Gnomad4 OTH exome AF: 0.00522

GnomAD4 genome AF: 0.0175 AC: 2666 AN: 152358 Hom.: 92 Cov.: 34 AF XY: 0.0169 AC XY: 1258 AN XY: 74500

Gnomad4 AFR AF: 0.0600

Gnomad4 AMR AF: 0.00718

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000514

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.00874 Hom.: 22

Bravo AF: 0.0202

Asia WGS AF: 0.00520 AC: 18 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 22, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
Cadd	Benign	0.95
Dann	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

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

Other links and lift over

dbSNP: rs34554642; hg19: chr17-78858816; COSMIC: COSV60805221;