17-80625855-G-T

Variant names:

• chr17-80625855-G-T
• rs901065
• NM_020761.3:c.265+62G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.265+62G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.333 in 1,196,144 control chromosomes in the GnomAD database, including 68,001 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 0.35 (9709 hom., cov: 32)
  • Exomes 𝑓: 0.33 (58292 hom.)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 8 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.43 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.265+62G>T		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.265+62G>T		intron	N/A	NP_001156506.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.265+62G>T		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000570891.5	TSL:1	c.265+62G>T		intron	N/A	ENSP00000460136.1
	RPTOR	ENST00000697423.1		c.319+62G>T		intron	N/A	ENSP00000513305.1

Frequencies

GnomAD3 genomes AF: 0.352 AC: 53441 AN: 151760 Hom.: 9703 Cov.: 32

Gnomad AFR AF: 0.435

Gnomad AMI AF: 0.262

Gnomad AMR AF: 0.302

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.221

Gnomad FIN AF: 0.248

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.348

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.330 AC: 345045 AN: 1044266 Hom.: 58292 AF XY: 0.327 AC XY: 175512 AN XY: 537522

African (AFR) AF: 0.438 AC: 11272 AN: 25746

American (AMR) AF: 0.233 AC: 10203 AN: 43768

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 6721 AN: 23304

East Asian (EAS) AF: 0.304 AC: 11543 AN: 37940

South Asian (SAS) AF: 0.233 AC: 18125 AN: 77690

European-Finnish (FIN) AF: 0.273 AC: 14332 AN: 52566

Middle Eastern (MID) AF: 0.330 AC: 1107 AN: 3352

European-Non Finnish (NFE) AF: 0.350 AC: 256779 AN: 733448

Other (OTH) AF: 0.322 AC: 14963 AN: 46452

GnomAD4 genome AF: 0.352 AC: 53470 AN: 151878 Hom.: 9709 Cov.: 32 AF XY: 0.344 AC XY: 25530 AN XY: 74230

African (AFR) AF: 0.435 AC: 18007 AN: 41410

American (AMR) AF: 0.302 AC: 4612 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1022 AN: 3472

East Asian (EAS) AF: 0.280 AC: 1434 AN: 5128

South Asian (SAS) AF: 0.220 AC: 1061 AN: 4812

European-Finnish (FIN) AF: 0.248 AC: 2616 AN: 10556

Middle Eastern (MID) AF: 0.350 AC: 103 AN: 294

European-Non Finnish (NFE) AF: 0.348 AC: 23638 AN: 67916

Other (OTH) AF: 0.350 AC: 739 AN: 2110

Alfa AF: 0.314 Hom.: 3533

Bravo AF: 0.357

Asia WGS AF: 0.218 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		0.058
Mutation Taster		=100/0	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: rs901065; hg19: chr17-78599655; COSMIC: COSV60802427;