7-116699082-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The ENST00000456159.1(MET):c.55A>T(p.Ile19Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/13 in silico tools predict a benign outcome for this variant. 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. I19T) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000456159.1 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.-3A>T | 5_prime_UTR_variant | Exon 2 of 21 | ENST00000397752.8 | NP_000236.2 |
Ensembl
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Not observed in large population cohorts (Lek et al., 2016); Has not been previously published as pathogenic or benign to our knowledge; Describes a nucleotide substitution 3 base pairs upstream of the ATG translational start site of the MET gene, occurring in the Kozak sequence, the conserved nucleotides just upstream of the ATG start codon, which play a major role in the initiation of translation -
Hereditary cancer-predisposing syndrome Uncertain:1
The c.-3A>T variant is located in the 5' untranslated region (5’ UTR) of the MET gene. This variant results from an A to T substitution 3 bases upstream from the first translated codon. Based on nucleotide sequence alignment, this position is well conserved in available vertebrate species. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.