17-80965614-C-T

Variant names:

• chr17-80965614-C-T
• rs3751932
• NM_020761.3:c.*1284C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.928 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.*1284C>T		3_prime_UTR	Exon 34 of 34	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.*1284C>T		3_prime_UTR	Exon 30 of 30	NP_001156506.1	Q8N122-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.*1284C>T		3_prime_UTR	Exon 34 of 34	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000575542.5	TSL:1	n.4779C>T		non_coding_transcript_exon	Exon 30 of 30
	RPTOR	ENST00000697423.1		c.*1284C>T		3_prime_UTR	Exon 34 of 34	ENSP00000513305.1	A0A8V8TMD9

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

African (AFR) AF: 0.926 AC: 3609 AN: 3898

American (AMR) AF: 0.931 AC: 2327 AN: 2500

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 4167 AN: 5128

East Asian (EAS) AF: 0.871 AC: 9940 AN: 11408

South Asian (SAS) AF: 0.913 AC: 643 AN: 704

European-Finnish (FIN) AF: 0.984 AC: 61 AN: 62

Middle Eastern (MID) AF: 0.848 AC: 417 AN: 492

European-Non Finnish (NFE) AF: 0.913 AC: 45673 AN: 50044

Other (OTH) AF: 0.907 AC: 6142 AN: 6774

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

African (AFR) AF: 0.935 AC: 38879 AN: 41562

American (AMR) AF: 0.920 AC: 14087 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.811 AC: 2815 AN: 3472

East Asian (EAS) AF: 0.859 AC: 4437 AN: 5166

South Asian (SAS) AF: 0.908 AC: 4382 AN: 4824

European-Finnish (FIN) AF: 0.891 AC: 9454 AN: 10610

Middle Eastern (MID) AF: 0.857 AC: 252 AN: 294

European-Non Finnish (NFE) AF: 0.913 AC: 62119 AN: 68030

Other (OTH) AF: 0.904 AC: 1911 AN: 2114

Alfa AF: 0.908 Hom.: 119994

Bravo AF: 0.913

Asia WGS AF: 0.906 AC: 3152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.042
DANN	Benign	0.67
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs3751932; hg19: chr17-78939414;