rs1064261

Variant summary

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

The NM_004958.4(MTOR):c.2997C>T(p.Asn999=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.728 in 1,613,694 control chromosomes in the GnomAD database, including 433,703 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 34109 hom., cov: 31)

Exomes 𝑓: 0.74 ( 399594 hom. )

Consequence

MTOR
NM_004958.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.749

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 1-11228701-G-A is Benign according to our data. Variant chr1-11228701-G-A is described in ClinVar as [Benign]. Clinvar id is 1170840.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-11228701-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.749 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.89 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.2997C>T	p.Asn999=	synonymous_variant	19/58	ENST00000361445.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTOR	ENST00000361445.9 linkuse as main transcript	c.2997C>T	p.Asn999=	synonymous_variant	19/58	1	NM_004958.4	P1

Frequencies

GnomAD3 genomes

AF:

0.649

AC:

98586

AN:

151888

Hom.:

34091

Cov.:

show subpopulations

Gnomad AFR

AF:

0.386

Gnomad AMI

AF:

0.755

Gnomad AMR

AF:

0.780

Gnomad ASJ

AF:

0.655

Gnomad EAS

AF:

0.912

Gnomad SAS

AF:

0.831

Gnomad FIN

AF:

0.745

Gnomad MID

AF:

0.744

Gnomad NFE

AF:

0.728

Gnomad OTH

AF:

0.696

GnomAD3 exomes

AF:

0.751

AC:

188750

AN:

251254

Hom.:

72781

AF XY:

0.755

AC XY:

102488

AN XY:

135792

show subpopulations

Gnomad AFR exome

AF:

0.373

Gnomad AMR exome

AF:

0.863

Gnomad ASJ exome

AF:

0.657

Gnomad EAS exome

AF:

0.919

Gnomad SAS exome

AF:

0.827

Gnomad FIN exome

AF:

0.746

Gnomad NFE exome

AF:

0.733

Gnomad OTH exome

AF:

0.747

GnomAD4 exome

AF:

0.736

AC:

1075646

AN:

1461688

Hom.:

399594

Cov.:

AF XY:

0.738

AC XY:

536691

AN XY:

727158

show subpopulations

Gnomad4 AFR exome

AF:

0.365

Gnomad4 AMR exome

AF:

0.852

Gnomad4 ASJ exome

AF:

0.657

Gnomad4 EAS exome

AF:

0.900

Gnomad4 SAS exome

AF:

0.824

Gnomad4 FIN exome

AF:

0.747

Gnomad4 NFE exome

AF:

0.731

Gnomad4 OTH exome

AF:

0.729

GnomAD4 genome

AF:

0.649

AC:

98648

AN:

152006

Hom.:

34109

Cov.:

AF XY:

0.656

AC XY:

48775

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.386

Gnomad4 AMR

AF:

0.781

Gnomad4 ASJ

AF:

0.655

Gnomad4 EAS

AF:

0.912

Gnomad4 SAS

AF:

0.831

Gnomad4 FIN

AF:

0.745

Gnomad4 NFE

AF:

0.728

Gnomad4 OTH

AF:

0.700

Alfa

AF:

0.685

Hom.:

20962

Bravo

AF:

0.639

Asia WGS

AF:

0.854

AC:

2970

AN:

3478

EpiCase

AF:

0.726

EpiControl

AF:

0.731

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jul 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

Macrocephaly-intellectual disability-neurodevelopmental disorder-small thorax syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

Cadd

Benign

2.8

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