NM_020761.3:c.1518A>G

Variant names:

• chr17-80880423-A-G
• rs2289759
• NM_020761.3:c.1518A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020761.3(RPTOR):​c.1518A>G​(p.Gln506Gln) 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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 28 publications found

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

Our verdict: Benign. The variant received -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.

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.1518A>G	p.Gln506Gln	synonymous	Exon 14 of 34	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.1510-11297A>G		intron	N/A	NP_001156506.1	Q8N122-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.1518A>G	p.Gln506Gln	synonymous	Exon 14 of 34	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000575542.5	TSL:1	n.1005A>G		non_coding_transcript_exon	Exon 10 of 30
	RPTOR	ENST00000697423.1		c.1572A>G	p.Gln524Gln	synonymous	Exon 14 of 34	ENSP00000513305.1	A0A8V8TMD9

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

GnomAD2 exomes AF: 0.258 AC: 64765 AN: 251220 AF XY: 0.259

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 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

African (AFR) AF: 0.136 AC: 4567 AN: 33472

American (AMR) AF: 0.265 AC: 11847 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.253 AC: 6619 AN: 26130

East Asian (EAS) AF: 0.367 AC: 14549 AN: 39680

South Asian (SAS) AF: 0.266 AC: 22920 AN: 86242

European-Finnish (FIN) AF: 0.210 AC: 11154 AN: 53054

Middle Eastern (MID) AF: 0.241 AC: 1387 AN: 5764

European-Non Finnish (NFE) AF: 0.263 AC: 291804 AN: 1111282

Other (OTH) AF: 0.259 AC: 15637 AN: 60348

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

African (AFR) AF: 0.143 AC: 5918 AN: 41510

American (AMR) AF: 0.253 AC: 3872 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3466

East Asian (EAS) AF: 0.371 AC: 1909 AN: 5152

South Asian (SAS) AF: 0.284 AC: 1367 AN: 4814

European-Finnish (FIN) AF: 0.206 AC: 2186 AN: 10612

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17534 AN: 67990

Other (OTH) AF: 0.241 AC: 507 AN: 2108

Alfa AF: 0.250 Hom.: 7697

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.28
DANN	Benign	0.56
PhyloP100		-0.86
Mutation Taster		=99/1	polymorphism (auto)

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

Other links and lift over

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