chr17-80681576-T-A

Variant names:

• chr17-80681576-T-A
• rs35544492
• NM_020761.3:c.349-26265T>A

Variant summary

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

The NM_020761.3(RPTOR):​c.349-26265T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 139,754 control chromosomes in the GnomAD database, including 2,751 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 0.13 (2751 hom., cov: 26)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0760
• Publications: 1 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.349-26265T>A		intron_variant	Intron 3 of 33	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.349-26265T>A		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.349-26265T>A		intron_variant	Intron 3 of 33	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 18721 AN: 139644 Hom.: 2747 Cov.: 26

Gnomad AFR AF: 0.311

Gnomad AMI AF: 0.0430

Gnomad AMR AF: 0.0847

Gnomad ASJ AF: 0.0852

Gnomad EAS AF: 0.00237

Gnomad SAS AF: 0.0182

Gnomad FIN AF: 0.0391

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0847

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.134 AC: 18744 AN: 139754 Hom.: 2751 Cov.: 26 AF XY: 0.127 AC XY: 8716 AN XY: 68422

African (AFR) AF: 0.311 AC: 11059 AN: 35570

American (AMR) AF: 0.0846 AC: 1202 AN: 14216

Ashkenazi Jewish (ASJ) AF: 0.0852 AC: 275 AN: 3228

East Asian (EAS) AF: 0.00238 AC: 12 AN: 5050

South Asian (SAS) AF: 0.0179 AC: 83 AN: 4624

European-Finnish (FIN) AF: 0.0391 AC: 398 AN: 10168

Middle Eastern (MID) AF: 0.116 AC: 31 AN: 268

European-Non Finnish (NFE) AF: 0.0847 AC: 5403 AN: 63804

Other (OTH) AF: 0.125 AC: 243 AN: 1942

Alfa AF: 0.0287 Hom.: 19

Bravo AF: 0.171

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.69
DANN	Benign	0.71
PhyloP100		0.076
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: rs35544492; hg19: chr17-78655376;