rs982274920
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BS2
The NM_004958.4(MTOR):c.1394C>T(p.Pro465Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000805 in 1,613,968 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P465A) has been classified as Uncertain significance.
Frequency
Consequence
NM_004958.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MTOR | NM_004958.4 | c.1394C>T | p.Pro465Leu | missense_variant | 9/58 | ENST00000361445.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MTOR | ENST00000361445.9 | c.1394C>T | p.Pro465Leu | missense_variant | 9/58 | 1 | NM_004958.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461824Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727230
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74326
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 26, 2020 | This sequence change replaces proline with leucine at codon 465 of the MTOR protein (p.Pro465Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MTOR-related disease. In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at