rs34848699

Variant names:

• chr17-80883478-G-A
• rs34848699
• NM_020761.3:c.1644G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-80883478-G-A
• chr17-80883478-G-C

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_020761.3(RPTOR):​c.1644G>A​(p.Thr548Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00882 in 1,613,948 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0061 (5 hom., cov: 33)
  • Exomes 𝑓: 0.0091 (76 hom.)
• Consequence: RPTOR NM_020761.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.17
• 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 17-80883478-G-A is Benign according to our data. Variant chr17-80883478-G-A is described in ClinVar as Benign. ClinVar VariationId is 770450.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.17 with no splicing effect.
• BS2: High AC in GnomAd4 at 932 AD gene.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	NM_020761.3	MANE Select	c.1644G>A	p.Thr548Thr	synonymous	Exon 15 of 34	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.1510-8242G>A		intron	N/A	NP_001156506.1	Q8N122-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPTOR	ENST00000306801.8	TSL:1 MANE Select	c.1644G>A	p.Thr548Thr	synonymous	Exon 15 of 34	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000575542.5	TSL:1	n.1131G>A		non_coding_transcript_exon	Exon 11 of 30
	RPTOR	ENST00000697423.1		c.1698G>A	p.Thr566Thr	synonymous	Exon 15 of 34	ENSP00000513305.1	A0A8V8TMD9

Frequencies

GnomAD3 genomes AF: 0.00613 AC: 932 AN: 152134 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00602

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00166

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.0100

GnomAD2 exomes AF: 0.00570 AC: 1432 AN: 251414 AF XY: 0.00574

Gnomad AFR exome AF: 0.00191

Gnomad AMR exome AF: 0.00434

Gnomad ASJ exome AF: 0.00129

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00116

Gnomad NFE exome AF: 0.00987

Gnomad OTH exome AF: 0.00636

GnomAD4 exome AF: 0.00910 AC: 13295 AN: 1461696 Hom.: 76 Cov.: 32 AF XY: 0.00883 AC XY: 6422 AN XY: 727150

African (AFR) AF: 0.00143 AC: 48 AN: 33480

American (AMR) AF: 0.00463 AC: 207 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00149 AC: 39 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00155 AC: 134 AN: 86258

European-Finnish (FIN) AF: 0.00173 AC: 92 AN: 53316

Middle Eastern (MID) AF: 0.00919 AC: 53 AN: 5768

European-Non Finnish (NFE) AF: 0.0109 AC: 12160 AN: 1111930

Other (OTH) AF: 0.00931 AC: 562 AN: 60386

GnomAD4 genome AF: 0.00612 AC: 932 AN: 152252 Hom.: 5 Cov.: 33 AF XY: 0.00568 AC XY: 423 AN XY: 74422

African (AFR) AF: 0.00192 AC: 80 AN: 41562

American (AMR) AF: 0.00601 AC: 92 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00166 AC: 8 AN: 4812

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10608

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 713 AN: 68022

Other (OTH) AF: 0.00994 AC: 21 AN: 2112

Alfa AF: 0.00747 Hom.: 4

Bravo AF: 0.00601

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0110

EpiControl AF: 0.0106

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.14
DANN	Benign	0.50
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.010		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: rs34848699; hg19: chr17-78857278; COSMIC: COSV100155807;