dbSNP rs199612643: MTOR:p.Glu1610Gln (chr1-11144692-C-G) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

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

The NM_004958.4(MTOR):c.4828G>C(p.Glu1610Gln) 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. E1610A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

MTOR
NM_004958.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.45

Publications

7 publications found

Variant links:

Genes affected

MTOR (HGNC:3942): (mechanistic target of rapamycin kinase) The protein encoded by this gene belongs to a family of phosphatidylinositol kinase-related kinases. These kinases mediate cellular responses to stresses such as DNA damage and nutrient deprivation. This kinase is a component of two distinct complexes, mTORC1, which controls protein synthesis, cell growth and proliferation, and mTORC2, which is a regulator of the actin cytoskeleton, and promotes cell survival and cell cycle progression. This protein acts as the target for the cell-cycle arrest and immunosuppressive effects of the FKBP12-rapamycin complex. Inhibitors of mTOR are used in organ transplants as immunosuppressants, and are being evaluated for their therapeutic potential in SARS-CoV-2 infections. Mutations in this gene are associated with Smith-Kingsmore syndrome and somatic focal cortical dysplasia type II. The ANGPTL7 gene is located in an intron of this gene. [provided by RefSeq, Aug 2020]

MTOR links:

MTOR-AS1 (HGNC:40242): (MTOR antisense RNA 1)

MTOR-AS1 links:

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ACMG classification

Classification was made for transcript

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_004958.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTOR	NM_004958.4	MANE Select	c.4828G>C	p.Glu1610Gln	missense	Exon 34 of 58	NP_004949.1	P42345
MTOR	NM_001386500.1		c.4828G>C	p.Glu1610Gln	missense	Exon 34 of 58	NP_001373429.1	P42345
MTOR	NM_001386501.1		c.3580G>C	p.Glu1194Gln	missense	Exon 33 of 57	NP_001373430.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MTOR	ENST00000361445.9	TSL:1 MANE Select	c.4828G>C	p.Glu1610Gln	missense	Exon 34 of 58	ENSP00000354558.4	P42345
MTOR	ENST00000934315.1		c.4882G>C	p.Glu1628Gln	missense	Exon 34 of 58	ENSP00000604374.1
MTOR	ENST00000934312.1		c.4849G>C	p.Glu1617Gln	missense	Exon 34 of 58	ENSP00000604371.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Uncertain

0.088

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

Eigen

Pathogenic

0.94

Eigen_PC

Pathogenic

0.91

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.90

M_CAP

Uncertain

0.27

MetaRNN

Uncertain

0.70

MetaSVM

Uncertain

0.30

MutationAssessor

Uncertain

2.3

PhyloP100

7.4

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.6

REVEL

Uncertain

0.51

Sift

Uncertain

0.012

Sift4G

Uncertain

0.031

Polyphen

1.0

Vest4

0.64

MutPred

0.39

Gain of MoRF binding (P = 0.0329)

MVP

0.68

MPC

1.9

ClinPred

0.91

GERP RS

5.8

Varity_R

0.79

gMVP

0.43

Mutation Taster

=35/65

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over