Variant 1-11106656-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004958.4(MTOR):c.*829A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0321 in 1,105,044 control chromosomes in the GnomAD database, including 991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.059 ( 374 hom., cov: 32)

Exomes 𝑓: 0.028 ( 617 hom. )

Consequence

MTOR
NM_004958.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.593

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 1-11106656-T-C is Benign according to our data. Variant chr1-11106656-T-C is described in ClinVar as [Benign]. Clinvar id is 1237596.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTOR	NM_004958.4 linkuse as main transcript	c.*829A>G		3_prime_UTR_variant	58/58	ENST00000361445.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTOR	ENST00000361445.9 linkuse as main transcript	c.*829A>G		3_prime_UTR_variant	58/58	1	NM_004958.4	P1

Frequencies

GnomAD3 genomes

AF:

0.0590

AC:

8974

AN:

152168

Hom.:

369

Cov.:

show subpopulations

Gnomad AFR

AF:

0.107

Gnomad AMI

AF:

0.0242

Gnomad AMR

AF:

0.0614

Gnomad ASJ

AF:

0.0691

Gnomad EAS

AF:

0.0854

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.0530

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0233

Gnomad OTH

AF:

0.0664

GnomAD4 exome

AF:

0.0278

AC:

26517

AN:

952758

Hom.:

617

Cov.:

AF XY:

0.0280

AC XY:

12395

AN XY:

442320

show subpopulations

Gnomad4 AFR exome

AF:

0.115

Gnomad4 AMR exome

AF:

0.0680

Gnomad4 ASJ exome

AF:

0.0809

Gnomad4 EAS exome

AF:

0.0628

Gnomad4 SAS exome

AF:

0.110

Gnomad4 FIN exome

AF:

0.0486

Gnomad4 NFE exome

AF:

0.0207

Gnomad4 OTH exome

AF:

0.0483

GnomAD4 genome

AF:

0.0591

AC:

8994

AN:

152286

Hom.:

374

Cov.:

AF XY:

0.0615

AC XY:

4578

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.107

Gnomad4 AMR

AF:

0.0618

Gnomad4 ASJ

AF:

0.0691

Gnomad4 EAS

AF:

0.0854

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.0530

Gnomad4 NFE

AF:

0.0233

Gnomad4 OTH

AF:

0.0672

Alfa

AF:

0.0318

Hom.:

146

Bravo

AF:

0.0610

Asia WGS

AF:

0.111

AC:

386

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 23, 2019	This variant is associated with the following publications: (PMID: 29978580) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

8.5

DANN

Benign

0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over