17-80965614-C-T

Position:

• chr17-80965614-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.*1284C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.909 in 233,302 control chromosomes in the GnomAD database, including 96,480 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 0.91 (63587 hom., cov: 34)
  • Exomes 𝑓: 0.90 (32893 hom.)
• Consequence: RPTOR NM_020761.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.47

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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.*1284C>T		3_prime_UTR_variant	34/34	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.*1284C>T		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.*1284C>T		3_prime_UTR_variant	34/34	1	NM_020761.3	ENSP00000307272.3
RPTOR	ENST00000575542.5	n.4779C>T		non_coding_transcript_exon_variant	30/30	1
RPTOR	ENST00000697423.1	c.*1284C>T		3_prime_UTR_variant	34/34			ENSP00000513305.1
RPTOR	ENST00000544334.6	c.*1284C>T		3_prime_UTR_variant	30/30	5		ENSP00000442479.2

Frequencies

GnomAD3 genomes AF: 0.913 AC: 138994 AN: 152174 Hom.: 63528 Cov.: 34

Gnomad AFR AF: 0.935

Gnomad AMI AF: 0.850

Gnomad AMR AF: 0.920

Gnomad ASJ AF: 0.811

Gnomad EAS AF: 0.859

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.891

Gnomad MID AF: 0.854

Gnomad NFE AF: 0.913

Gnomad OTH AF: 0.903

GnomAD4 exome AF: 0.901 AC: 72979 AN: 81010 Hom.: 32893 Cov.: 0 AF XY: 0.898 AC XY: 33448 AN XY: 37244

Gnomad4 AFR exome AF: 0.926

Gnomad4 AMR exome AF: 0.931

Gnomad4 ASJ exome AF: 0.813

Gnomad4 EAS exome AF: 0.871

Gnomad4 SAS exome AF: 0.913

Gnomad4 FIN exome AF: 0.984

Gnomad4 NFE exome AF: 0.913

Gnomad4 OTH exome AF: 0.907

GnomAD4 genome AF: 0.913 AC: 139111 AN: 152292 Hom.: 63587 Cov.: 34 AF XY: 0.911 AC XY: 67813 AN XY: 74456

Gnomad4 AFR AF: 0.935

Gnomad4 AMR AF: 0.920

Gnomad4 ASJ AF: 0.811

Gnomad4 EAS AF: 0.859

Gnomad4 SAS AF: 0.908

Gnomad4 FIN AF: 0.891

Gnomad4 NFE AF: 0.913

Gnomad4 OTH AF: 0.904

Alfa AF: 0.907 Hom.: 88432

Bravo AF: 0.913

Asia WGS AF: 0.906 AC: 3152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.042
DANN	Benign	0.67
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.3

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: rs3751932; hg19: chr17-78939414;