rs1062935

chr17-80966057-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020761.3(RPTOR):c.*1727T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 230,630 control chromosomes in the GnomAD database, including 22,913 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 0.40 (13589 hom., cov: 27)
  • Exomes 𝑓: 0.48 (9324 hom.)
• Consequence: RPTOR NM_020761.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RPTOR	NM_020761.3	c.*1727T>C		3_prime_UTR_variant	34/34	ENST00000306801.8
RPTOR	NM_001163034.2	c.*1727T>C		3_prime_UTR_variant	30/30

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RPTOR	ENST00000306801.8	c.*1727T>C		3_prime_UTR_variant	34/34	1	NM_020761.3	P1
RPTOR	ENST00000575542.5	n.5222T>C		non_coding_transcript_exon_variant	30/30	1
RPTOR	ENST00000544334.6	c.*1727T>C		3_prime_UTR_variant	30/30	5
RPTOR	ENST00000697423.1	c.*1727T>C		3_prime_UTR_variant	34/34

Frequencies

GnomAD3 genomes AF: 0.401 AC: 60223 AN: 150248 Hom.: 13584 Cov.: 27

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.642

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.514

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.413

Gnomad FIN AF: 0.428

Gnomad MID AF: 0.352

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.427

GnomAD4 exome AF: 0.477 AC: 38267 AN: 80264 Hom.: 9324 Cov.: 0 AF XY: 0.475 AC XY: 17529 AN XY: 36906

Gnomad4 AFR exome AF: 0.199

Gnomad4 AMR exome AF: 0.548

Gnomad4 ASJ exome AF: 0.518

Gnomad4 EAS exome AF: 0.537

Gnomad4 SAS exome AF: 0.393

Gnomad4 FIN exome AF: 0.576

Gnomad4 NFE exome AF: 0.482

Gnomad4 OTH exome AF: 0.443

GnomAD4 genome AF: 0.401 AC: 60242 AN: 150366 Hom.: 13589 Cov.: 27 AF XY: 0.400 AC XY: 29286 AN XY: 73238

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.514

Gnomad4 EAS AF: 0.464

Gnomad4 SAS AF: 0.412

Gnomad4 FIN AF: 0.428

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.427

Alfa AF: 0.470 Hom.: 26496

Bravo AF: 0.404

Asia WGS AF: 0.407 AC: 1417 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	10
Dann	Benign	0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs1062935; hg19: chr17-78939857;