17-80584611-T-C

Position:

• chr17-80584611-T-C

Variant summary

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

The NM_020761.3(RPTOR):​c.162+38820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,136 control chromosomes in the GnomAD database, including 9,412 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 0.33 (9412 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52

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]

LOC105371922 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.162+38820T>C		intron_variant		ENST00000306801.8	NP_065812.1
LOC105371922	XR_007065932.1	n.138+2213A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.162+38820T>C		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50909 AN: 152018 Hom.: 9411 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.335 AC: 50924 AN: 152136 Hom.: 9412 Cov.: 32 AF XY: 0.328 AC XY: 24430 AN XY: 74374

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.321

Gnomad4 ASJ AF: 0.377

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.298

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.432

Gnomad4 OTH AF: 0.361

Alfa AF: 0.404 Hom.: 6014

Bravo AF: 0.327

Asia WGS AF: 0.259 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.075
DANN	Benign	0.46
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: rs12949279; hg19: chr17-78558411;