rs200524064
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_000245.4(MET):c.2548A>G(p.Ile850Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000929 in 1,613,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I850M) has been classified as Uncertain significance.
Frequency
Consequence
NM_000245.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.2548A>G | p.Ile850Val | missense_variant | 11/21 | ENST00000397752.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.2548A>G | p.Ile850Val | missense_variant | 11/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.2602A>G | p.Ile868Val | missense_variant | 11/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*153A>G | 3_prime_UTR_variant, NMD_transcript_variant | 10/20 | 1 | ||||
MET | ENST00000422097.2 | c.2548A>G | p.Ile850Val | missense_variant | 11/12 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000854 AC: 13AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248880Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 135016
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461664Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727132
GnomAD4 genome ? AF: 0.0000854 AC: 13AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74374
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 04, 2022 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with colon cancer (Yehia et al., 2018); This variant is associated with the following publications: (PMID: 24728327, 29684080) - |
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 24, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 16, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at