17-80947993-G-A

Variant names:

• chr17-80947993-G-A
• rs7502563
• NM_020761.3:c.3265+642G>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.3265+642G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,150 control chromosomes in the GnomAD database, including 10,039 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 0.34 (10039 hom., cov: 33)
• Consequence: RPTOR NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.435
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020761.3. 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.3265+642G>A		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.2791+642G>A		intron	N/A	NP_001156506.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.3265+642G>A		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000575542.5	TSL:1	n.2752+642G>A		intron	N/A
	RPTOR	ENST00000697423.1		c.3319+642G>A		intron	N/A	ENSP00000513305.1

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51915 AN: 152034 Hom.: 10032 Cov.: 33

Gnomad AFR AF: 0.159

Gnomad AMI AF: 0.282

Gnomad AMR AF: 0.393

Gnomad ASJ AF: 0.417

Gnomad EAS AF: 0.551

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.405

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.410

Gnomad OTH AF: 0.378

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

GnomAD4 genome AF: 0.341 AC: 51945 AN: 152150 Hom.: 10039 Cov.: 33 AF XY: 0.342 AC XY: 25462 AN XY: 74376

African (AFR) AF: 0.159 AC: 6597 AN: 41518

American (AMR) AF: 0.394 AC: 6020 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.417 AC: 1446 AN: 3470

East Asian (EAS) AF: 0.552 AC: 2857 AN: 5176

South Asian (SAS) AF: 0.348 AC: 1680 AN: 4824

European-Finnish (FIN) AF: 0.405 AC: 4283 AN: 10566

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.410 AC: 27897 AN: 67982

Other (OTH) AF: 0.379 AC: 799 AN: 2110

Alfa AF: 0.377 Hom.: 4471

Bravo AF: 0.333

Asia WGS AF: 0.419 AC: 1458 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.9
DANN	Benign	0.67
PhyloP100		-0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs7502563; hg19: chr17-78921793;