Genetic Variant MTOR:c.-141C>A (chr1-11262571-G-T) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_004958.4(MTOR):c.-141C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 152,180 control chromosomes in the GnomAD database, including 26,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 26456 hom., cov: 32)

Exomes 𝑓: 0.54 ( 9 hom. )

Consequence

MTOR
NM_004958.4 upstream_gene

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.116

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=-0.93).

BP6

Variant 1-11262571-G-T is Benign according to our data. Variant chr1-11262571-G-T is described in ClinVar as [Benign]. Clinvar id is 1167238.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTOR	NM_004958.4 link	c.-141C>A		upstream_gene_variant		ENST00000361445.9	NP_004949.1	P42345

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTOR	ENST00000361445.9 link	c.-141C>A		upstream_gene_variant		1	NM_004958.4	ENSP00000354558.4		P42345

Frequencies

GnomAD3 genomes

AF:

0.545

AC:

82845

AN:

151986

Hom.:

26447

Cov.:

show subpopulations

Gnomad AFR

AF:

0.182

Gnomad AMI

AF:

0.727

Gnomad AMR

AF:

0.638

Gnomad ASJ

AF:

0.585

Gnomad EAS

AF:

0.776

Gnomad SAS

AF:

0.637

Gnomad FIN

AF:

0.692

Gnomad MID

AF:

0.665

Gnomad NFE

AF:

0.692

Gnomad OTH

AF:

0.591

GnomAD4 exome

AF:

0.539

AC:

AN:

Hom.:

AF XY:

0.548

AC XY:

AN XY:

show subpopulations

Gnomad4 AFR exome

AF:

0.250

Gnomad4 FIN exome

AF:

0.500

Gnomad4 NFE exome

AF:

0.560

Gnomad4 OTH exome

AF:

0.625

GnomAD4 genome

AF:

0.545

AC:

82855

AN:

152104

Hom.:

26456

Cov.:

AF XY:

0.548

AC XY:

40733

AN XY:

74354

show subpopulations

Gnomad4 AFR

AF:

0.182

Gnomad4 AMR

AF:

0.638

Gnomad4 ASJ

AF:

0.585

Gnomad4 EAS

AF:

0.776

Gnomad4 SAS

AF:

0.638

Gnomad4 FIN

AF:

0.692

Gnomad4 NFE

AF:

0.692

Gnomad4 OTH

AF:

0.594

Alfa

AF:

0.596

Hom.:

3605

Bravo

AF:

0.528

Asia WGS

AF:

0.676

AC:

2350

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 20, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 23555892, 23209702, 25776475) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

5.5

DANN

Benign

0.39

Splicing

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