7-116757518-A-G
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_000245.4(MET):c.1944A>G(p.Gln648Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.189 in 1,612,994 control chromosomes in the GnomAD database, including 29,894 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Consequence
NM_000245.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -21 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
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MET | NM_000245.4 | c.1944A>G | p.Gln648Gln | synonymous_variant | Exon 7 of 21 | ENST00000397752.8 | NP_000236.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.1944A>G | p.Gln648Gln | synonymous_variant | Exon 7 of 21 | 1 | NM_000245.4 | ENSP00000380860.3 | ||
MET | ENST00000318493.11 | c.1944A>G | p.Gln648Gln | synonymous_variant | Exon 7 of 21 | 1 | ENSP00000317272.6 | |||
MET | ENST00000436117.3 | n.1944A>G | non_coding_transcript_exon_variant | Exon 7 of 20 | 1 | ENSP00000410980.2 | ||||
MET | ENST00000422097.2 | c.1944A>G | p.Gln648Gln | synonymous_variant | Exon 7 of 12 | 3 | ENSP00000398776.2 |
Frequencies
GnomAD3 genomes AF: 0.171 AC: 26008AN: 152034Hom.: 2342 Cov.: 32
GnomAD3 exomes AF: 0.182 AC: 45494AN: 249296Hom.: 4535 AF XY: 0.188 AC XY: 25453AN XY: 135246
GnomAD4 exome AF: 0.191 AC: 278297AN: 1460842Hom.: 27553 Cov.: 33 AF XY: 0.193 AC XY: 139975AN XY: 726788
GnomAD4 genome AF: 0.171 AC: 26013AN: 152152Hom.: 2341 Cov.: 32 AF XY: 0.171 AC XY: 12756AN XY: 74380
ClinVar
Submissions by phenotype
not specified Benign:5
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This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Papillary renal cell carcinoma type 1 Benign:3
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
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not provided Benign:2
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Variant summary: The MET c.1944A>G (p.Gln648Gln) variant causes a synonymous change involving a non-conserved nucleotide with 5/5 splice prediction tools predicting no significant impact on splicing. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 22638/120534 (1/5, 2318 homozygotes), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic MET variant of 1/666666, suggesting this variant is likely a benign polymorphism. Multiple reputable clinical laboratories have cited the variant as "benign." Therefore, the variant of interest has been classified as Benign. -
Renal cell carcinoma Benign:1
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Hereditary cancer-predisposing syndrome Benign:1
This alteration is classified as 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at