rs3751934

Positions:

• chr17-80964698-C-A
• chr17-80964698-C-T

Variant summary

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

The NM_020761.3(RPTOR):​c.*368C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 299,672 control chromosomes in the GnomAD database, including 33,661 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 0.49 (19303 hom., cov: 33)
  • Exomes 𝑓: 0.43 (14358 hom.)
• Consequence: RPTOR NM_020761.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.*368C>A		3_prime_UTR_variant	34/34	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.*368C>A		3_prime_UTR_variant	30/30		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.*368C>A		3_prime_UTR_variant	34/34	1	NM_020761.3	ENSP00000307272.3
RPTOR	ENST00000575542.5	n.3863C>A		non_coding_transcript_exon_variant	30/30	1
RPTOR	ENST00000697423.1	c.*368C>A		3_prime_UTR_variant	34/34			ENSP00000513305.1
RPTOR	ENST00000544334.6	c.*368C>A		3_prime_UTR_variant	30/30	5		ENSP00000442479.2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74211 AN: 151918 Hom.: 19264 Cov.: 33

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.431 AC: 63598 AN: 147636 Hom.: 14358 Cov.: 0 AF XY: 0.429 AC XY: 31418 AN XY: 73152

Gnomad4 AFR exome AF: 0.674

Gnomad4 AMR exome AF: 0.544

Gnomad4 ASJ exome AF: 0.392

Gnomad4 EAS exome AF: 0.432

Gnomad4 SAS exome AF: 0.467

Gnomad4 FIN exome AF: 0.422

Gnomad4 NFE exome AF: 0.406

Gnomad4 OTH exome AF: 0.429

GnomAD4 genome AF: 0.489 AC: 74304 AN: 152036 Hom.: 19303 Cov.: 33 AF XY: 0.487 AC XY: 36177 AN XY: 74322

Gnomad4 AFR AF: 0.675

Gnomad4 AMR AF: 0.520

Gnomad4 ASJ AF: 0.385

Gnomad4 EAS AF: 0.380

Gnomad4 SAS AF: 0.455

Gnomad4 FIN AF: 0.393

Gnomad4 NFE AF: 0.402

Gnomad4 OTH AF: 0.459

Alfa AF: 0.408 Hom.: 17820

Bravo AF: 0.506

Asia WGS AF: 0.407 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.66
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs3751934; hg19: chr17-78938498;