rs12951309

Variant names:

• chr17-80584486-G-A
• rs12951309
• NM_020761.3:c.162+38695G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):​c.162+38695G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,022 control chromosomes in the GnomAD database, including 3,001 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 0.19 (3001 hom., cov: 31)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.10
• Publications: 7 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]

LOC105371922 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.264 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.162+38695G>A		intron	N/A	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.162+38695G>A		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.162+38695G>A		intron	N/A	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000570891.5	TSL:1	c.162+38695G>A		intron	N/A	ENSP00000460136.1	Q8N122-2
	RPTOR	ENST00000697423.1		c.216+38695G>A		intron	N/A	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28627 AN: 151904 Hom.: 3000 Cov.: 31

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.238

Gnomad OTH AF: 0.205

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

GnomAD4 genome AF: 0.188 AC: 28635 AN: 152022 Hom.: 3001 Cov.: 31 AF XY: 0.187 AC XY: 13918 AN XY: 74288

African (AFR) AF: 0.0880 AC: 3652 AN: 41498

American (AMR) AF: 0.192 AC: 2934 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 704 AN: 3472

East Asian (EAS) AF: 0.276 AC: 1424 AN: 5154

South Asian (SAS) AF: 0.196 AC: 943 AN: 4814

European-Finnish (FIN) AF: 0.200 AC: 2107 AN: 10552

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.238 AC: 16201 AN: 67958

Other (OTH) AF: 0.202 AC: 426 AN: 2106

Alfa AF: 0.220 Hom.: 12762

Bravo AF: 0.182

Asia WGS AF: 0.182 AC: 637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.0040
DANN	Benign	0.68
PhyloP100		-3.1
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: rs12951309; hg19: chr17-78558286;