rs17848553

chr1-11130673-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 4.63

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]

ACMG classification

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	UniProt
MTOR	NM_004958.4	c.5469C>T	p.Ala1823=	synonymous_variant	39/58	ENST00000361445.9

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4380 AN: 152050 Hom.: 162 Cov.: 32

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

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.: 32 AF XY: 0.00990 AC XY: 7189 AN XY: 725976

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.: 32 AF XY: 0.0305 AC XY: 2268 AN XY: 74396

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.: 20

Bravo AF: 0.0336

Asia WGS AF: 0.0620 AC: 218 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -

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

Other links and lift over

dbSNP: rs17848553; hg19: chr1-11190730; COSMIC: COSV63869835; COSMIC: COSV63869835;