NM_020761.3:c.760A>C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RPTOR NM_020761.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.24

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RPTOR	NM_020761.3	c.760A>C	p.Met254Leu	missense_variant	Exon 6 of 34	ENST00000306801.8	NP_065812.1
RPTOR	NM_001163034.2	c.760A>C	p.Met254Leu	missense_variant	Exon 6 of 30		NP_001156506.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RPTOR	ENST00000306801.8	c.760A>C	p.Met254Leu	missense_variant	Exon 6 of 34	1	NM_020761.3	ENSP00000307272.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D;D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.60	D;D;D
MetaSVM	Benign	-0.86	T
MutationAssessor	Benign	1.4	L;L;L
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-2.3	.;N;D
REVEL	Benign	0.24
Sift	Benign	0.078	.;T;T
Sift4G	Benign	0.22	T;T;T
Polyphen		0.070	.;B;.
Vest4		0.72
MutPred		0.31		Loss of disorder (P = 0.3037);Loss of disorder (P = 0.3037);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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-78727915;