17-80584611-T-C

Variant names:

• chr17-80584611-T-C
• rs12949279
• NM_020761.3:c.162+38820T>C

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+38820T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.335 in 152,136 control chromosomes in the GnomAD database, including 9,412 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 0.33 (9412 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.52
• Publications: 9 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 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+38820T>C		intron	N/A	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.162+38820T>C		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+38820T>C		intron	N/A	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000570891.5	TSL:1	c.162+38820T>C		intron	N/A	ENSP00000460136.1	Q8N122-2
	RPTOR	ENST00000697423.1		c.216+38820T>C		intron	N/A	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50909 AN: 152018 Hom.: 9411 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.411

Gnomad AMR AF: 0.321

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.432

Gnomad OTH AF: 0.365

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

GnomAD4 genome AF: 0.335 AC: 50924 AN: 152136 Hom.: 9412 Cov.: 32 AF XY: 0.328 AC XY: 24430 AN XY: 74374

African (AFR) AF: 0.187 AC: 7770 AN: 41528

American (AMR) AF: 0.321 AC: 4902 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1308 AN: 3470

East Asian (EAS) AF: 0.309 AC: 1598 AN: 5164

South Asian (SAS) AF: 0.298 AC: 1435 AN: 4820

European-Finnish (FIN) AF: 0.315 AC: 3332 AN: 10580

Middle Eastern (MID) AF: 0.367 AC: 108 AN: 294

European-Non Finnish (NFE) AF: 0.432 AC: 29335 AN: 67980

Other (OTH) AF: 0.361 AC: 761 AN: 2110

Alfa AF: 0.402 Hom.: 6700

Bravo AF: 0.327

Asia WGS AF: 0.259 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.075
DANN	Benign	0.46
PhyloP100		-3.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		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: rs12949279; hg19: chr17-78558411;