1-11226121-T-C

Variant names:

• chr1-11226121-T-C
• rs12124983
• NM_004958.4:c.3030+2547A>G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004958.4(MTOR):​c.3030+2547A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.552 in 152,066 control chromosomes in the GnomAD database, including 27,195 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.55 (27195 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: MTOR NM_004958.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.416

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]

RNU6-291P (HGNC:47254): (RNA, U6 small nuclear 291, pseudogene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.761 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MTOR	NM_004958.4	c.3030+2547A>G		intron_variant	Intron 19 of 57	ENST00000361445.9	NP_004949.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MTOR	ENST00000361445.9	c.3030+2547A>G		intron_variant	Intron 19 of 57	1	NM_004958.4	ENSP00000354558.4

Frequencies

GnomAD3 genomes AF: 0.553 AC: 83970 AN: 151948 Hom.: 27188 Cov.: 32

Gnomad AFR AF: 0.184

Gnomad AMI AF: 0.730

Gnomad AMR AF: 0.645

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.781

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.693

Gnomad MID AF: 0.687

Gnomad NFE AF: 0.704

Gnomad OTH AF: 0.599

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.552 AC: 83978 AN: 152066 Hom.: 27195 Cov.: 32 AF XY: 0.555 AC XY: 41265 AN XY: 74332

Gnomad4 AFR AF: 0.184

Gnomad4 AMR AF: 0.645

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.781

Gnomad4 SAS AF: 0.644

Gnomad4 FIN AF: 0.693

Gnomad4 NFE AF: 0.704

Gnomad4 OTH AF: 0.602

Alfa AF: 0.616 Hom.: 5366

Bravo AF: 0.535

Asia WGS AF: 0.677 AC: 2351 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	6.5
DANN	Benign	0.84

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: rs12124983; hg19: chr1-11286178;