rs571156267
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4BP6_Very_StrongBS1BS2
The NM_004958.4(MTOR):βc.5490_5501delβ(p.Thr1834_Thr1837del) variant causes a inframe deletion change. The variant allele was found at a frequency of 0.000646 in 1,613,568 control chromosomes in the GnomAD database, including 5 homozygotes. Variant has been reported in ClinVar as Benign (β β ). Synonymous variant affecting the same amino acid position (i.e. T1830T) has been classified as Likely benign.
Frequency
Genomes: π 0.00059 ( 1 hom., cov: 32)
Exomes π: 0.00065 ( 4 hom. )
Consequence
MTOR
NM_004958.4 inframe_deletion
NM_004958.4 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 3.78
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_004958.4.
BP6
?
Variant 1-11130640-CGTGGTGGCGGCA-C is Benign according to our data. Variant chr1-11130640-CGTGGTGGCGGCA-C is described in ClinVar as [Benign]. Clinvar id is 414898.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000585 (89/152044) while in subpopulation EAS AF= 0.00775 (40/5160). AF 95% confidence interval is 0.00585. There are 1 homozygotes in gnomad4. There are 41 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 89 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTOR | NM_004958.4 | c.5490_5501del | p.Thr1834_Thr1837del | inframe_deletion | 39/58 | ENST00000361445.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTOR | ENST00000361445.9 | c.5490_5501del | p.Thr1834_Thr1837del | inframe_deletion | 39/58 | 1 | NM_004958.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000586 AC: 89AN: 151926Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.00111 AC: 275AN: 247814Hom.: 3 AF XY: 0.00110 AC XY: 147AN XY: 134238
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GnomAD4 exome AF: 0.000652 AC: 953AN: 1461524Hom.: 4 AF XY: 0.000686 AC XY: 499AN XY: 727062
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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 | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2024 | MTOR: BS1, BS2 - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 30, 2023 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 28, 2020 | - - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at