Variant 1-11144726-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_004958.4(MTOR):c.4794G>A(p.Glu1598=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MTOR
NM_004958.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.09

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-AS1 (HGNC:40242): (MTOR antisense RNA 1)

MTOR-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 1-11144726-C-T is Benign according to our data. Variant chr1-11144726-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3046635.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=3.09 with no splicing effect.

BS2

High AC in GnomAdExome4 at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTOR	NM_004958.4 linkuse as main transcript	c.4794G>A	p.Glu1598=	synonymous_variant	34/58	ENST00000361445.9
MTOR-AS1	NR_046600.1 linkuse as main transcript	n.150C>T		non_coding_transcript_exon_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTOR	ENST00000361445.9 linkuse as main transcript	c.4794G>A	p.Glu1598=	synonymous_variant	34/58	1	NM_004958.4	P1
MTOR-AS1	ENST00000445982.5 linkuse as main transcript	n.150C>T		non_coding_transcript_exon_variant	2/4	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250888

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135656

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000980

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461408

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727046

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000812

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

MTOR-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 16, 2023

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.94

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