17-80880423-A-G

Position:

• chr17-80880423-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020761.3(RPTOR):​c.1518A>G​(p.Gln506=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.257 in 1,612,836 control chromosomes in the GnomAD database, including 54,709 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 0.23 (4096 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50613 hom.)
• Consequence: RPTOR NM_020761.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.857

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP7: Synonymous conserved (PhyloP=-0.857 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.1518A>G	p.Gln506=	synonymous_variant	14/34	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.1510-11297A>G		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.1518A>G	p.Gln506=	synonymous_variant	14/34	1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34373 AN: 152032 Hom.: 4092 Cov.: 32

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.207

Gnomad AMR AF: 0.253

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.283

Gnomad FIN AF: 0.206

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.241

GnomAD3 exomes AF: 0.258 AC: 64765 AN: 251220 Hom.: 8787 AF XY: 0.259 AC XY: 35189 AN XY: 135844

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.269

Gnomad ASJ exome AF: 0.254

Gnomad EAS exome AF: 0.383

Gnomad SAS exome AF: 0.264

Gnomad FIN exome AF: 0.208

Gnomad NFE exome AF: 0.260

Gnomad OTH exome AF: 0.257

GnomAD4 exome AF: 0.260 AC: 380484 AN: 1460686 Hom.: 50613 Cov.: 33 AF XY: 0.261 AC XY: 189433 AN XY: 726686

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.265

Gnomad4 ASJ exome AF: 0.253

Gnomad4 EAS exome AF: 0.367

Gnomad4 SAS exome AF: 0.266

Gnomad4 FIN exome AF: 0.210

Gnomad4 NFE exome AF: 0.263

Gnomad4 OTH exome AF: 0.259

GnomAD4 genome AF: 0.226 AC: 34392 AN: 152150 Hom.: 4096 Cov.: 32 AF XY: 0.226 AC XY: 16845 AN XY: 74388

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.253

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.371

Gnomad4 SAS AF: 0.284

Gnomad4 FIN AF: 0.206

Gnomad4 NFE AF: 0.258

Gnomad4 OTH AF: 0.241

Alfa AF: 0.253 Hom.: 6399

Bravo AF: 0.225

Asia WGS AF: 0.310 AC: 1077 AN: 3478

EpiCase AF: 0.264

EpiControl AF: 0.266

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.28
DANN	Benign	0.56

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: rs2289759; hg19: chr17-78854223; COSMIC: COSV60803658;