Variant rs17848553 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.5469C>T(p.Ala1823=) variant causes a synonymous change. The variant allele was found at a frequency of 0.0107 in 1,611,908 control chromosomes in the GnomAD database, including 596 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 165 hom., cov: 32)

Exomes 𝑓: 0.0088 ( 431 hom. )

Consequence

MTOR
NM_004958.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.63

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=-0.5).

BP6

Variant 1-11130673-G-A is Benign according to our data. Variant chr1-11130673-G-A is described in ClinVar as [Benign]. Clinvar id is 414896.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11130673-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0673 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MTOR	NM_004958.4 linkuse as main transcript	c.5469C>T	p.Ala1823=	synonymous_variant	39/58	ENST00000361445.9	NP_004949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTOR	ENST00000361445.9 linkuse as main transcript	c.5469C>T	p.Ala1823=	synonymous_variant	39/58	1	NM_004958.4	ENSP00000354558	P1

Frequencies

GnomAD3 genomes

AF:

0.0288

AC:

4380

AN:

152050

Hom.:

162

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0645

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0708

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0446

Gnomad SAS

AF:

0.0666

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000397

Gnomad OTH

AF:

0.0225

GnomAD3 exomes

AF:

0.0249

AC:

6041

AN:

242338

Hom.:

197

AF XY:

0.0236

AC XY:

3103

AN XY:

131330

show subpopulations

Gnomad AFR exome

AF:

0.0668

Gnomad AMR exome

AF:

0.0674

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0413

Gnomad SAS exome

AF:

0.0609

Gnomad FIN exome

AF:

0.0000476

Gnomad NFE exome

AF:

0.000398

Gnomad OTH exome

AF:

0.0180

GnomAD4 exome

AF:

0.00882

AC:

12870

AN:

1459740

Hom.:

431

Cov.:

AF XY:

0.00990

AC XY:

7189

AN XY:

725976

show subpopulations

Gnomad4 AFR exome

AF:

0.0667

Gnomad4 AMR exome

AF:

0.0660

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0375

Gnomad4 SAS exome

AF:

0.0585

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000274

Gnomad4 OTH exome

AF:

0.0147

GnomAD4 genome

AF:

0.0289

AC:

4404

AN:

152168

Hom.:

165

Cov.:

AF XY:

0.0305

AC XY:

2268

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0649

Gnomad4 AMR

AF:

0.0708

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0447

Gnomad4 SAS

AF:

0.0660

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000397

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00966

Hom.:

Bravo

AF:

0.0336

Asia WGS

AF:

0.0620

AC:

218

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.50

CADD

Benign

6.2

DANN

Benign

0.53

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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