NM_020761.3:c.760A>C

Variant names:

• chr17-80754115-A-C
• rs2066656852
• NM_020761.3:c.760A>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_020761.3(RPTOR):​c.760A>C​(p.Met254Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M254V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPTOR NM_020761.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.24
• Publications: 0 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.760A>C	p.Met254Leu	missense	Exon 6 of 34	NP_065812.1	Q8N122-1
	RPTOR	NM_001163034.2		c.760A>C	p.Met254Leu	missense	Exon 6 of 30	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.760A>C	p.Met254Leu	missense	Exon 6 of 34	ENSP00000307272.3	Q8N122-1
	RPTOR	ENST00000570891.5	TSL:1	c.760A>C	p.Met254Leu	missense	Exon 6 of 9	ENSP00000460136.1	Q8N122-2
	RPTOR	ENST00000575542.5	TSL:1	n.247A>C		non_coding_transcript_exon	Exon 2 of 30

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Uncertain	0.091	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	23
DANN	Uncertain	0.97
DEOGEN2	Uncertain	0.72	D
Eigen	Uncertain	0.27
Eigen_PC	Uncertain	0.42
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.98	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L
PhyloP100		9.2
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.24
Sift	Benign	0.078	T
Sift4G	Benign	0.22	T
Polyphen		0.070	B
Vest4		0.72
MutPred		0.31		Loss of disorder (P = 0.3037)
MVP		0.64
MPC		1.8
ClinPred		0.89	D
GERP RS		5.7
Varity_R		0.58
gMVP		0.67

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: rs2066656852; hg19: chr17-78727915;