chr7-116775060-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP3
The ENST00000397752.8(MET):c.3208G>T(p.Val1070Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000821 in 1,461,860 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. V1070M) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000397752.8 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.3208G>T | p.Val1070Leu | missense_variant | 15/21 | ENST00000397752.8 | NP_000236.2 | |
MET | NM_001127500.3 | c.3262G>T | p.Val1088Leu | missense_variant | 15/21 | NP_001120972.1 | ||
MET | NM_001324402.2 | c.1918G>T | p.Val640Leu | missense_variant | 14/20 | NP_001311331.1 | ||
MET | XM_011516223.2 | c.3265G>T | p.Val1089Leu | missense_variant | 16/22 | XP_011514525.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.3208G>T | p.Val1070Leu | missense_variant | 15/21 | 1 | NM_000245.4 | ENSP00000380860 | P3 | |
MET | ENST00000318493.11 | c.3262G>T | p.Val1088Leu | missense_variant | 15/21 | 1 | ENSP00000317272 | A2 | ||
MET | ENST00000436117.3 | c.*813G>T | 3_prime_UTR_variant, NMD_transcript_variant | 14/20 | 1 | ENSP00000410980 | ||||
MET | ENST00000454623.1 | c.463G>T | p.Val155Leu | missense_variant | 3/3 | 5 | ENSP00000398140 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461860Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727236
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 30, 2024 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1088 of the MET protein (p.Val1088Leu). This variant is not present in population databases (gnomAD no frequency). 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: 958823). 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 not expected to disrupt MET protein function with a negative 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 11, 2023 | The p.V1088L variant (also known as c.3262G>T), located in coding exon 14 of the MET gene, results from a G to T substitution at nucleotide position 3262. The valine at codon 1088 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. 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