17-80952150-T-C

Variant names:

• chr17-80952150-T-C
• rs6420481
• NM_020761.3:c.3370+2603T>C

Variant summary

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

The NM_020761.3(RPTOR):​c.3370+2603T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.516 in 152,102 control chromosomes in the GnomAD database, including 21,442 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 0.52 (21442 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.34
• Publications: 7 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.695 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.3370+2603T>C		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.2896+2603T>C		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.3370+2603T>C		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000575542.5	TSL:1	n.2857+2603T>C		intron	N/A
	RPTOR	ENST00000697423.1		c.3424+2603T>C		intron	N/A	ENSP00000513305.1

Frequencies

GnomAD3 genomes AF: 0.516 AC: 78434 AN: 151982 Hom.: 21407 Cov.: 33

Gnomad AFR AF: 0.702

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.466

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.556

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.436

Gnomad OTH AF: 0.519

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.516 AC: 78525 AN: 152102 Hom.: 21442 Cov.: 33 AF XY: 0.513 AC XY: 38120 AN XY: 74328

African (AFR) AF: 0.702 AC: 29096 AN: 41468

American (AMR) AF: 0.466 AC: 7133 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.477 AC: 1655 AN: 3470

East Asian (EAS) AF: 0.556 AC: 2869 AN: 5160

South Asian (SAS) AF: 0.419 AC: 2021 AN: 4828

European-Finnish (FIN) AF: 0.435 AC: 4601 AN: 10576

Middle Eastern (MID) AF: 0.435 AC: 128 AN: 294

European-Non Finnish (NFE) AF: 0.436 AC: 29660 AN: 67986

Other (OTH) AF: 0.518 AC: 1092 AN: 2110

Alfa AF: 0.454 Hom.: 9854

Bravo AF: 0.526

Asia WGS AF: 0.494 AC: 1719 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.95
DANN	Benign	0.53
PhyloP100		-1.3
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: rs6420481; hg19: chr17-78925950;