rs571156267

Positions:

• chr1-11130640-CGTGGTGGCGGCA-C
• chr1-11130640-CGTGGTGGCGGCA-CGTGGTGGCGGCAGTGGTGGCGGCA

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM4 BP6_Very_Strong BS1 BS2

The NM_004958.4(MTOR):​c.5490_5501del​(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 (★★). Synonymous variant affecting the same amino acid position (i.e. T1830T) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00059 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00065 (4 hom.)
• Consequence: MTOR NM_004958.4 inframe_deletion
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• 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]

ACMG classification

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: 89 AN: 151926 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000725

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00773

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000589

Gnomad OTH AF: 0.000959

GnomAD3 exomes AF: 0.00111 AC: 275 AN: 247814 Hom.: 3 AF XY: 0.00110 AC XY: 147 AN XY: 134238

Gnomad AFR exome AF: 0.000186

Gnomad AMR exome AF: 0.0000290

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0107

Gnomad SAS exome AF: 0.000459

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000506

Gnomad OTH exome AF: 0.000657

GnomAD4 exome AF: 0.000652 AC: 953 AN: 1461524 Hom.: 4 AF XY: 0.000686 AC XY: 499 AN XY: 727062

Gnomad4 AFR exome AF: 0.000209

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00504

Gnomad4 SAS exome AF: 0.000406

Gnomad4 FIN exome AF: 0.0000562

Gnomad4 NFE exome AF: 0.000592

Gnomad4 OTH exome AF: 0.000745

GnomAD4 genome AF: 0.000585 AC: 89 AN: 152044 Hom.: 1 Cov.: 32 AF XY: 0.000552 AC XY: 41 AN XY: 74334

Gnomad4 AFR AF: 0.0000723

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00775

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000589

Gnomad4 OTH AF: 0.000949

Alfa AF: 0.000400 Hom.: 0

Bravo AF: 0.000778

EpiCase AF: 0.000600

EpiControl AF: 0.000653

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

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

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs571156267; hg19: chr1-11190697;