ENST00000575542.5:n.3863C>A

Variant names:

• chr17-80964698-C-A
• rs3751934
• ENST00000575542.5:n.3863C>A

Variant summary

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

The ENST00000575542.5(RPTOR):​n.3863C>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 299,672 control chromosomes in the GnomAD database, including 33,661 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 0.49 (19303 hom., cov: 33)
  • Exomes 𝑓: 0.43 (14358 hom.)
• Consequence: RPTOR ENST00000575542.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.625
• Publications: 21 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.668 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.*368C>A		3_prime_UTR_variant	Exon 34 of 34	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.*368C>A		3_prime_UTR_variant	Exon 30 of 30		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000575542.5	n.3863C>A		non_coding_transcript_exon_variant	Exon 30 of 30	1
RPTOR	ENST00000306801.8	c.*368C>A		3_prime_UTR_variant	Exon 34 of 34	1	NM_020761.3	ENSP00000307272.3
RPTOR	ENST00000697423.1	c.*368C>A		3_prime_UTR_variant	Exon 34 of 34			ENSP00000513305.1
RPTOR	ENST00000544334.6	c.*368C>A		3_prime_UTR_variant	Exon 30 of 30	5		ENSP00000442479.2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74211 AN: 151918 Hom.: 19264 Cov.: 33

Gnomad AFR AF: 0.675

Gnomad AMI AF: 0.376

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.380

Gnomad SAS AF: 0.455

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.402

Gnomad OTH AF: 0.461

GnomAD4 exome AF: 0.431 AC: 63598 AN: 147636 Hom.: 14358 Cov.: 0 AF XY: 0.429 AC XY: 31418 AN XY: 73152

African (AFR) AF: 0.674 AC: 4143 AN: 6146

American (AMR) AF: 0.544 AC: 3329 AN: 6122

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 2625 AN: 6700

East Asian (EAS) AF: 0.432 AC: 6205 AN: 14378

South Asian (SAS) AF: 0.467 AC: 4928 AN: 10550

European-Finnish (FIN) AF: 0.422 AC: 1395 AN: 3302

Middle Eastern (MID) AF: 0.410 AC: 311 AN: 758

European-Non Finnish (NFE) AF: 0.406 AC: 36296 AN: 89496

Other (OTH) AF: 0.429 AC: 4366 AN: 10184

GnomAD4 genome AF: 0.489 AC: 74304 AN: 152036 Hom.: 19303 Cov.: 33 AF XY: 0.487 AC XY: 36177 AN XY: 74322

African (AFR) AF: 0.675 AC: 27973 AN: 41460

American (AMR) AF: 0.520 AC: 7947 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1337 AN: 3470

East Asian (EAS) AF: 0.380 AC: 1952 AN: 5142

South Asian (SAS) AF: 0.455 AC: 2192 AN: 4822

European-Finnish (FIN) AF: 0.393 AC: 4159 AN: 10584

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.402 AC: 27332 AN: 67952

Other (OTH) AF: 0.459 AC: 970 AN: 2112

Alfa AF: 0.419 Hom.: 26579

Bravo AF: 0.506

Asia WGS AF: 0.407 AC: 1420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.18
DANN	Benign	0.66
PhyloP100		-0.63
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3751934; hg19: chr17-78938498;