17-80687523-G-A

Position:

• chr17-80687523-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.349-20318G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0901 in 152,276 control chromosomes in the GnomAD database, including 701 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 0.090 (701 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.186

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.134 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.349-20318G>A		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.349-20318G>A		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.349-20318G>A		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.0900 AC: 13691 AN: 152158 Hom.: 697 Cov.: 33

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.0538

Gnomad ASJ AF: 0.0772

Gnomad EAS AF: 0.0559

Gnomad SAS AF: 0.0735

Gnomad FIN AF: 0.0569

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.0790

Gnomad OTH AF: 0.0772

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

GnomAD4 genome AF: 0.0901 AC: 13717 AN: 152276 Hom.: 701 Cov.: 33 AF XY: 0.0880 AC XY: 6548 AN XY: 74446

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.0536

Gnomad4 ASJ AF: 0.0772

Gnomad4 EAS AF: 0.0558

Gnomad4 SAS AF: 0.0742

Gnomad4 FIN AF: 0.0569

Gnomad4 NFE AF: 0.0790

Gnomad4 OTH AF: 0.0764

Alfa AF: 0.0776 Hom.: 583

Bravo AF: 0.0927

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.81
DANN	Benign	0.51
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9901366; hg19: chr17-78661323;