chr7-116699594-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_000245.4(MET):āc.510C>Gā(p.Ser170Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,866 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 ā ). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S170G) 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.510C>G | p.Ser170Arg | missense_variant | 2/21 | ENST00000397752.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.510C>G | p.Ser170Arg | missense_variant | 2/21 | 1 | NM_000245.4 | P3 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000809 AC: 2AN: 247344Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134228
GnomAD4 exome AF: 0.0000137 AC: 20AN: 1461712Hom.: 0 Cov.: 32 AF XY: 0.0000151 AC XY: 11AN XY: 727150
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74326
ClinVar
Submissions by phenotype
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 21, 2024 | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 170 of the MET protein (p.Ser170Arg). This variant is present in population databases (rs587778442, gnomAD 0.004%). 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: 134647). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 22, 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; Identified in healthy individuals undergoing whole genome sequencing (Bodian et al., 2014); This variant is associated with the following publications: (PMID: 24728327) - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2024 | The p.S170R variant (also known as c.510C>G), located in coding exon 1 of the MET gene, results from a C to G substitution at nucleotide position 510. The serine at codon 170 is replaced by arginine, an amino acid with dissimilar properties. This variant was identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS One, 2014 May;9:e94554). 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. - |
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