chr17-80661010-C-A

Variant names:

• chr17-80661010-C-A
• rs12939076
• NM_020761.3:c.348+17200C>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.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 NM_020761.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.852
• Publications: 4 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.229 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.348+17200C>A		intron	N/A	NP_065812.1
	RPTOR	NM_001163034.2		c.348+17200C>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.348+17200C>A		intron	N/A	ENSP00000307272.3
	RPTOR	ENST00000570891.5	TSL:1	c.348+17200C>A		intron	N/A	ENSP00000460136.1
	RPTOR	ENST00000697423.1		c.402+17200C>A		intron	N/A	ENSP00000513305.1

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

African (AFR) AF: 0.0493 AC: 2049 AN: 41550

American (AMR) AF: 0.181 AC: 2774 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 689 AN: 3470

East Asian (EAS) AF: 0.239 AC: 1233 AN: 5154

South Asian (SAS) AF: 0.205 AC: 990 AN: 4820

European-Finnish (FIN) AF: 0.194 AC: 2060 AN: 10596

Middle Eastern (MID) AF: 0.202 AC: 59 AN: 292

European-Non Finnish (NFE) AF: 0.233 AC: 15799 AN: 67952

Other (OTH) AF: 0.193 AC: 407 AN: 2114

Alfa AF: 0.196 Hom.: 1668

Bravo AF: 0.165

Asia WGS AF: 0.163 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.65
PhyloP100		0.85
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97
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: rs12939076; hg19: chr17-78634810;