rs2295080

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004958.4(MTOR):c.-141C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,180 control chromosomes in the GnomAD database, including 26,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 26456 hom., cov: 32)

Exomes 𝑓: 0.54 ( 9 hom. )

Consequence

MTOR
NM_004958.4 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.116

Publications

98 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 Gene-Disease associations (from GenCC):

macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Illumina
overgrowth syndrome and/or cerebral malformations due to abnormalities in MTOR pathway genes
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen

MTOR links:

ENSG00000309051 (HGNC:):

ENSG00000309051 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-11262571-G-T is Benign according to our data. Variant chr1-11262571-G-T is described in ClinVar as Benign. ClinVar VariationId is 1167238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

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	Effect	Exon Rank	Protein	UniProt
MTOR	NM_004958.4	MANE Select	c.-141C>A	upstream_gene	N/A	NP_004949.1	P42345
MTOR	NM_001386500.1		c.-168C>A	upstream_gene	N/A	NP_001373429.1	P42345
MTOR	NM_001386501.1		c.-1280C>A	upstream_gene	N/A	NP_001373430.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MTOR	ENST00000361445.9	TSL:1 MANE Select	c.-141C>A	upstream_gene	N/A	ENSP00000354558.4	P42345
MTOR	ENST00000934315.1		c.-141C>A	upstream_gene	N/A	ENSP00000604374.1
MTOR	ENST00000934312.1		c.-141C>A	upstream_gene	N/A	ENSP00000604371.1

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82845

AN:

151986

Hom.:

26447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.637

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.591

GnomAD4 exome

AF:

0.539

AC:

AN:

Hom.:

AF XY:

0.548

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.500

AC:

AN:

European-Non Finnish (NFE)

AF:

0.560

AC:

AN:

Other (OTH)

AF:

0.625

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.545

AC:

82855

AN:

152104

Hom.:

26456

Cov.:

AF XY:

0.548

AC XY:

40733

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.182

AC:

7542

AN:

41526

American (AMR)

AF:

0.638

AC:

9749

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.585

AC:

2029

AN:

3470

East Asian (EAS)

AF:

0.776

AC:

3997

AN:

5152

South Asian (SAS)

AF:

0.638

AC:

3079

AN:

4826

European-Finnish (FIN)

AF:

0.692

AC:

7326

AN:

10584

Middle Eastern (MID)

AF:

0.677

AC:

199

AN:

294

European-Non Finnish (NFE)

AF:

0.692

AC:

47020

AN:

67956

Other (OTH)

AF:

0.594

AC:

1254

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1573

3147

4720

6294

7867

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.579

Hom.:

3617

Bravo

AF:

0.528

Asia WGS

AF:

0.676

AC:

2350

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.5

(source)

DANN

Benign

0.39

PhyloP100

0.12

PromoterAI

-0.25

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over