rs1062935

Variant names:

• chr17-80966057-T-C
• rs1062935
• ENST00000575542.5:n.5222T>C

Variant summary

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

The ENST00000575542.5(RPTOR):​n.5222T>C 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 0.427 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 ENST00000575542.5 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 33 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]

ENSG00000261924 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000575542.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.*1727T>C		3_prime_UTR	Exon 34 of 34	NP_065812.1
	RPTOR	NM_001163034.2		c.*1727T>C		3_prime_UTR	Exon 30 of 30	NP_001156506.1
	LOC400627	NR_148968.1		n.*182A>G		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000575542.5	TSL:1	n.5222T>C		non_coding_transcript_exon	Exon 30 of 30
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.*1727T>C		3_prime_UTR	Exon 34 of 34	ENSP00000307272.3
	RPTOR	ENST00000697423.1		c.*1727T>C		3_prime_UTR	Exon 34 of 34	ENSP00000513305.1

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

African (AFR) AF: 0.199 AC: 771 AN: 3868

American (AMR) AF: 0.548 AC: 1351 AN: 2466

Ashkenazi Jewish (ASJ) AF: 0.518 AC: 2628 AN: 5076

East Asian (EAS) AF: 0.537 AC: 6091 AN: 11340

South Asian (SAS) AF: 0.393 AC: 274 AN: 698

European-Finnish (FIN) AF: 0.576 AC: 38 AN: 66

Middle Eastern (MID) AF: 0.496 AC: 241 AN: 486

European-Non Finnish (NFE) AF: 0.482 AC: 23913 AN: 49576

Other (OTH) AF: 0.443 AC: 2960 AN: 6688

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

African (AFR) AF: 0.191 AC: 7857 AN: 41078

American (AMR) AF: 0.522 AC: 7891 AN: 15116

Ashkenazi Jewish (ASJ) AF: 0.514 AC: 1777 AN: 3454

East Asian (EAS) AF: 0.464 AC: 2281 AN: 4914

South Asian (SAS) AF: 0.412 AC: 1964 AN: 4764

European-Finnish (FIN) AF: 0.428 AC: 4349 AN: 10156

Middle Eastern (MID) AF: 0.344 AC: 99 AN: 288

European-Non Finnish (NFE) AF: 0.482 AC: 32558 AN: 67616

Other (OTH) AF: 0.427 AC: 886 AN: 2076

Alfa AF: 0.460 Hom.: 58506

Bravo AF: 0.404

Asia WGS AF: 0.407 AC: 1417 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	10
DANN	Benign	0.84
PhyloP100		0.077
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: rs1062935; hg19: chr17-78939857;