rs201191014
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_000245.4(MET):āc.1048A>Cā(p.Lys350Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,688 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K350E) 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 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.1048A>C | p.Lys350Gln | missense_variant | 2/21 | ENST00000397752.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.1048A>C | p.Lys350Gln | missense_variant | 2/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.1048A>C | p.Lys350Gln | missense_variant | 2/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.1048A>C | p.Lys350Gln | missense_variant, NMD_transcript_variant | 2/20 | 1 | |||
MET | ENST00000422097.2 | c.1048A>C | p.Lys350Gln | missense_variant | 2/12 | 3 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000418 AC: 1AN: 239376Hom.: 0 AF XY: 0.00000772 AC XY: 1AN XY: 129532
GnomAD4 exome AF: 6.90e-7 AC: 1AN: 1449688Hom.: 0 Cov.: 32 AF XY: 0.00000139 AC XY: 1AN XY: 719864
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Feb 06, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 41609). This variant is present in population databases (rs201191014, ExAC 0.002%). This sequence change replaces lysine with glutamine at codon 350 of the MET protein (p.Lys350Gln). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and glutamine. - |
not provided Uncertain:1
Uncertain significance, no assertion criteria provided | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jul 13, 2012 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at