chr1-11107422-G-A

Position:

• chr1-11107422-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004958.4(MTOR):​c.*63C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000617 in 1,581,448 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0033 (2 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (3 hom.)
• Consequence: MTOR NM_004958.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.72

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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.69).
• BP6: Variant 1-11107422-G-A is Benign according to our data. Variant chr1-11107422-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1189891.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00328 (499/152242) while in subpopulation AFR AF= 0.0113 (471/41528). AF 95% confidence interval is 0.0105. There are 2 homozygotes in gnomad4. There are 236 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 499 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MTOR	NM_004958.4	c.*63C>T		3_prime_UTR_variant	58/58	ENST00000361445.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MTOR	ENST00000361445.9	c.*63C>T		3_prime_UTR_variant	58/58	1	NM_004958.4	P1

Frequencies

GnomAD3 genomes AF: 0.00329 AC: 500 AN: 152124 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.0114

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00137

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00239

GnomAD4 exome AF: 0.000333 AC: 476 AN: 1429206 Hom.: 3 Cov.: 31 AF XY: 0.000284 AC XY: 202 AN XY: 710796

Gnomad4 AFR exome AF: 0.0122

Gnomad4 AMR exome AF: 0.000717

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000253

Gnomad4 SAS exome AF: 0.0000249

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000816

Gnomad4 OTH exome AF: 0.00102

GnomAD4 genome AF: 0.00328 AC: 499 AN: 152242 Hom.: 2 Cov.: 32 AF XY: 0.00317 AC XY: 236 AN XY: 74438

Gnomad4 AFR AF: 0.0113

Gnomad4 AMR AF: 0.00137

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000294

Gnomad4 OTH AF: 0.00237

Alfa AF: 0.00236 Hom.: 0

Bravo AF: 0.00371

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.69
CADD	Benign	15
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs79536981; hg19: chr1-11167479;