Variant chr1-11212411-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004958.4(MTOR):c.3462G>C(p.Arg1154Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00738 in 1,614,122 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. R1154R) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.011 ( 68 hom., cov: 32)

Exomes 𝑓: 0.0070 ( 344 hom. )

Consequence

MTOR
NM_004958.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.223

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 (HGNC:):

MTOR links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 1-11212411-C-G is Benign according to our data. Variant chr1-11212411-C-G is described in ClinVar as [Benign]. Clinvar id is 414901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11212411-C-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.223 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0612 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.3462G>C	p.Arg1154Arg	synonymous_variant	23/58	ENST00000361445.9	NP_004949.1	P42345

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MTOR	ENST00000361445.9 linkuse as main transcript	c.3462G>C	p.Arg1154Arg	synonymous_variant	23/58	1	NM_004958.4	ENSP00000354558.4		P42345

Frequencies

GnomAD3 genomes

AF:

0.0112

AC:

1706

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00316

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0645

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0449

Gnomad SAS

AF:

0.0655

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0198

AC:

4976

AN:

251248

Hom.:

169

AF XY:

0.0200

AC XY:

2713

AN XY:

135778

show subpopulations

Gnomad AFR exome

AF:

0.00295

Gnomad AMR exome

AF:

0.0641

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0411

Gnomad SAS exome

AF:

0.0600

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000211

Gnomad OTH exome

AF:

0.0153

GnomAD4 exome

AF:

0.00698

AC:

10208

AN:

1461850

Hom.:

344

Cov.:

AF XY:

0.00832

AC XY:

6050

AN XY:

727228

show subpopulations

Gnomad4 AFR exome

AF:

0.00311

Gnomad4 AMR exome

AF:

0.0624

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0375

Gnomad4 SAS exome

AF:

0.0581

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.0102

GnomAD4 genome

AF:

0.0112

AC:

1708

AN:

152272

Hom.:

Cov.:

AF XY:

0.0140

AC XY:

1041

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00322

Gnomad4 AMR

AF:

0.0645

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0450

Gnomad4 SAS

AF:

0.0649

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00992

Alfa

AF:

0.00192

Hom.:

Bravo

AF:

0.0132

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

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	clinical testing	GeneDx	Aug 17, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
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

-0.51

CADD

Benign

8.7

DANN

Benign

0.70

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

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