17-80698990-C-T

Variant names:

• chr17-80698990-C-T
• rs12948054
• NM_020761.3:c.349-8851C>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.349-8851C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0629 in 152,294 control chromosomes in the GnomAD database, including 389 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 0.063 (389 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.93
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0986 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.349-8851C>T		intron_variant	Intron 3 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.349-8851C>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.349-8851C>T		intron_variant	Intron 3 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.0630 AC: 9580 AN: 152176 Hom.: 389 Cov.: 33

Gnomad AFR AF: 0.0188

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.0496

Gnomad ASJ AF: 0.0536

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0161

Gnomad FIN AF: 0.0681

Gnomad MID AF: 0.0538

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.0780

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

GnomAD4 genome AF: 0.0629 AC: 9580 AN: 152294 Hom.: 389 Cov.: 33 AF XY: 0.0588 AC XY: 4375 AN XY: 74468

African (AFR) AF: 0.0188 AC: 781 AN: 41572

American (AMR) AF: 0.0495 AC: 758 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0536 AC: 186 AN: 3472

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0159 AC: 77 AN: 4830

European-Finnish (FIN) AF: 0.0681 AC: 724 AN: 10624

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.101 AC: 6839 AN: 67994

Other (OTH) AF: 0.0772 AC: 163 AN: 2112

Alfa AF: 0.0855 Hom.: 1085

Bravo AF: 0.0599

Asia WGS AF: 0.00722 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.62
DANN	Benign	0.43
PhyloP100		-2.9
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: rs12948054; hg19: chr17-78672790;