17-80625855-G-T

Position:

• chr17-80625855-G-T

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.265+62G>T		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.265+62G>T		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.265+62G>T		intron_variant		1	NM_020761.3	ENSP00000307272.3

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

Gnomad4 AFR exome AF: 0.438

Gnomad4 AMR exome AF: 0.233

Gnomad4 ASJ exome AF: 0.288

Gnomad4 EAS exome AF: 0.304

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.273

Gnomad4 NFE exome AF: 0.350

Gnomad4 OTH exome AF: 0.322

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

Gnomad4 AFR AF: 0.435

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.248

Gnomad4 NFE AF: 0.348

Gnomad4 OTH AF: 0.350

Alfa AF: 0.310 Hom.: 3028

Bravo AF: 0.357

Asia WGS AF: 0.218 AC: 761 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.6
DANN	Benign	0.74

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: rs901065; hg19: chr17-78599655; COSMIC: COSV60802427;