7-116796096-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000245.4(MET):c.4145G>C(p.Arg1382Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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. R1382L) has been classified as Likely benign.
Frequency
Consequence
NM_000245.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.4145G>C | p.Arg1382Pro | missense_variant | 21/21 | ENST00000397752.8 | |
MET | NM_001127500.3 | c.4199G>C | p.Arg1400Pro | missense_variant | 21/21 | ||
MET | NM_001324402.2 | c.2855G>C | p.Arg952Pro | missense_variant | 20/20 | ||
MET | XM_011516223.2 | c.4202G>C | p.Arg1401Pro | missense_variant | 22/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.4145G>C | p.Arg1382Pro | missense_variant | 21/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.4199G>C | p.Arg1400Pro | missense_variant | 21/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*1750G>C | 3_prime_UTR_variant, NMD_transcript_variant | 20/20 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.00 AC: 0AN: 152164Hom.: 0 Cov.: 32 FAILED QC
GnomAD4 exome Cov.: 32
GnomAD4 genome ? Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74454
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 97 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 25, 2023 | - - |
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 08, 2023 | This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 1400 of the MET protein (p.Arg1400Pro). 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: 569622). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Aug 03, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2023 | The p.R1400P variant (also known as c.4199G>C), located in coding exon 20 of the MET gene, results from a G to C substitution at nucleotide position 4199. The arginine at codon 1400 is replaced by proline, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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