chr17-80553095-C-T

Variant names:

• chr17-80553095-C-T
• rs12950635
• NM_020761.3:c.162+7304C>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.162+7304C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.165 in 152,260 control chromosomes in the GnomAD database, including 2,361 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 0.16 (2361 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.35
• Publications: 3 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=-0.97).
• 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+7304C>T		intron	N/A	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.162+7304C>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.162+7304C>T		intron	N/A	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000570891.5	TSL:1	c.162+7304C>T		intron	N/A	ENSP00000460136.1	Q8N122-2
	RPTOR	ENST00000697423.1		c.216+7304C>T		intron	N/A	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25051 AN: 152142 Hom.: 2360 Cov.: 33

Gnomad AFR AF: 0.0623

Gnomad AMI AF: 0.203

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.276

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.203

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.178

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

GnomAD4 genome AF: 0.165 AC: 25060 AN: 152260 Hom.: 2361 Cov.: 33 AF XY: 0.165 AC XY: 12281 AN XY: 74444

African (AFR) AF: 0.0627 AC: 2608 AN: 41572

American (AMR) AF: 0.173 AC: 2646 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 660 AN: 3470

East Asian (EAS) AF: 0.276 AC: 1431 AN: 5178

South Asian (SAS) AF: 0.190 AC: 919 AN: 4830

European-Finnish (FIN) AF: 0.181 AC: 1922 AN: 10608

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.210 AC: 14260 AN: 68004

Other (OTH) AF: 0.175 AC: 369 AN: 2110

Alfa AF: 0.0985 Hom.: 175

Bravo AF: 0.158

Asia WGS AF: 0.177 AC: 617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.41
DANN	Benign	0.41
PhyloP100		-1.4
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: rs12950635; hg19: chr17-78526895;