rs12939076

Positions:

• chr17-80661010-C-A
• chr17-80661010-C-T

Variant summary

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

The ENST00000306801.8(RPTOR):​c.348+17200C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 152,154 control chromosomes in the GnomAD database, including 2,705 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 0.17 (2705 hom., cov: 32)
• Consequence: RPTOR ENST00000306801.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.852

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.348+17200C>A		intron_variant		ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.348+17200C>A		intron_variant			NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.348+17200C>A		intron_variant		1	NM_020761.3	ENSP00000307272	P1

Frequencies

GnomAD3 genomes AF: 0.173 AC: 26253 AN: 152036 Hom.: 2708 Cov.: 32

Gnomad AFR AF: 0.0494

Gnomad AMI AF: 0.199

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.239

Gnomad SAS AF: 0.206

Gnomad FIN AF: 0.194

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.233

Gnomad OTH AF: 0.196

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

GnomAD4 genome AF: 0.172 AC: 26241 AN: 152154 Hom.: 2705 Cov.: 32 AF XY: 0.172 AC XY: 12809 AN XY: 74386

Gnomad4 AFR AF: 0.0493

Gnomad4 AMR AF: 0.181

Gnomad4 ASJ AF: 0.199

Gnomad4 EAS AF: 0.239

Gnomad4 SAS AF: 0.205

Gnomad4 FIN AF: 0.194

Gnomad4 NFE AF: 0.233

Gnomad4 OTH AF: 0.193

Alfa AF: 0.195 Hom.: 1460

Bravo AF: 0.165

Asia WGS AF: 0.163 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.65
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

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: rs12939076; hg19: chr17-78634810;