NM_020761.3:c.349-16236C>T

Variant names:

• chr17-80691605-C-T
• rs9906827
• NM_020761.3:c.349-16236C>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.349-16236C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,050 control chromosomes in the GnomAD database, including 13,265 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 0.41 (13265 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.17
• Publications: 14 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=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.349-16236C>T		intron_variant	Intron 3 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.349-16236C>T		intron_variant	Intron 3 of 29		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.349-16236C>T		intron_variant	Intron 3 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.409 AC: 62101 AN: 151932 Hom.: 13267 Cov.: 32

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.358

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.431

Gnomad FIN AF: 0.495

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.460

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.408 AC: 62106 AN: 152050 Hom.: 13265 Cov.: 32 AF XY: 0.410 AC XY: 30480 AN XY: 74324

African (AFR) AF: 0.290 AC: 12048 AN: 41476

American (AMR) AF: 0.357 AC: 5459 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3468

East Asian (EAS) AF: 0.569 AC: 2937 AN: 5162

South Asian (SAS) AF: 0.431 AC: 2078 AN: 4820

European-Finnish (FIN) AF: 0.495 AC: 5231 AN: 10568

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.460 AC: 31260 AN: 67954

Other (OTH) AF: 0.439 AC: 927 AN: 2112

Alfa AF: 0.435 Hom.: 24241

Bravo AF: 0.392

Asia WGS AF: 0.437 AC: 1523 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.061
DANN	Benign	0.65
PhyloP100		-3.2
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: rs9906827; hg19: chr17-78665405;