NM_020761.3:c.348+28053C>T

Variant names:

• chr17-80671863-C-T
• rs7217223
• NM_020761.3:c.348+28053C>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.348+28053C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.279 in 151,932 control chromosomes in the GnomAD database, including 5,994 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 0.28 (5994 hom., cov: 32)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.383
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.348+28053C>T		intron_variant	Intron 3 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.348+28053C>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.348+28053C>T		intron_variant	Intron 3 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.279 AC: 42312 AN: 151814 Hom.: 5988 Cov.: 32

Gnomad AFR AF: 0.248

Gnomad AMI AF: 0.294

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.333

Gnomad EAS AF: 0.359

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.240

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.282

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

GnomAD4 genome AF: 0.279 AC: 42330 AN: 151932 Hom.: 5994 Cov.: 32 AF XY: 0.280 AC XY: 20766 AN XY: 74258

African (AFR) AF: 0.248 AC: 10267 AN: 41412

American (AMR) AF: 0.205 AC: 3127 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.333 AC: 1155 AN: 3466

East Asian (EAS) AF: 0.359 AC: 1856 AN: 5170

South Asian (SAS) AF: 0.297 AC: 1429 AN: 4816

European-Finnish (FIN) AF: 0.339 AC: 3568 AN: 10526

Middle Eastern (MID) AF: 0.234 AC: 68 AN: 290

European-Non Finnish (NFE) AF: 0.294 AC: 19995 AN: 67958

Other (OTH) AF: 0.284 AC: 598 AN: 2102

Alfa AF: 0.269 Hom.: 2887

Bravo AF: 0.268

Asia WGS AF: 0.318 AC: 1107 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.61
DANN	Benign	0.52
PhyloP100		-0.38
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: rs7217223; hg19: chr17-78645663;