chr7-116763126-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The NM_000245.4(MET):c.2441C>T(p.Pro814Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. P814T) has been classified as Uncertain significance.
Frequency
Consequence
NM_000245.4 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.2441C>T | p.Pro814Leu | missense_variant | 11/21 | ENST00000397752.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.2441C>T | p.Pro814Leu | missense_variant | 11/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.2495C>T | p.Pro832Leu | missense_variant | 11/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*46C>T | 3_prime_UTR_variant, NMD_transcript_variant | 10/20 | 1 | ||||
MET | ENST00000422097.2 | c.2441C>T | p.Pro814Leu | missense_variant | 11/12 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249252Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135214
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461782Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 727190
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74308
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 01, 2024 | The p.P832L variant (also known as c.2495C>T), located in coding exon 10 of the MET gene, results from a C to T substitution at nucleotide position 2495. The proline at codon 832 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Jun 24, 2021 | - - |
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 16, 2024 | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 832 of the MET protein (p.Pro832Leu). This variant is present in population databases (rs781452657, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 524888). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MET protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at