17-80946120-C-T

Variant names:

• chr17-80946120-C-T
• rs2271612
• NM_020761.3:c.3140+339C>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.3140+339C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 151,930 control chromosomes in the GnomAD database, including 20,889 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 0.52 (20889 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.07
• Publications: 8 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 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.3140+339C>T		intron	N/A	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.2666+339C>T		intron	N/A	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.3140+339C>T		intron	N/A	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000575542.5	TSL:1	n.2627+339C>T		intron	N/A
	RPTOR	ENST00000697423.1		c.3194+339C>T		intron	N/A	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.520 AC: 78985 AN: 151812 Hom.: 20865 Cov.: 32

Gnomad AFR AF: 0.555

Gnomad AMI AF: 0.685

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.559

Gnomad MID AF: 0.561

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.505

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

GnomAD4 genome AF: 0.520 AC: 79047 AN: 151930 Hom.: 20889 Cov.: 32 AF XY: 0.519 AC XY: 38494 AN XY: 74234

African (AFR) AF: 0.555 AC: 22978 AN: 41392

American (AMR) AF: 0.546 AC: 8333 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1842 AN: 3472

East Asian (EAS) AF: 0.290 AC: 1496 AN: 5154

South Asian (SAS) AF: 0.397 AC: 1911 AN: 4818

European-Finnish (FIN) AF: 0.559 AC: 5886 AN: 10538

Middle Eastern (MID) AF: 0.541 AC: 158 AN: 292

European-Non Finnish (NFE) AF: 0.511 AC: 34762 AN: 67966

Other (OTH) AF: 0.500 AC: 1056 AN: 2112

Alfa AF: 0.506 Hom.: 14073

Bravo AF: 0.524

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.49
DANN	Benign	0.73
PhyloP100		-1.1
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: rs2271612; hg19: chr17-78919920;