chr7-116795666-C-T
Variant summary
Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS1
The NM_000245.4(MET):c.3810C>T(p.Gly1270=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000339 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. G1270G) has been classified as Likely benign.
Frequency
Consequence
NM_000245.4 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -17 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.3810C>T | p.Gly1270= | synonymous_variant | 20/21 | ENST00000397752.8 | |
MET | NM_001127500.3 | c.3864C>T | p.Gly1288= | synonymous_variant | 20/21 | ||
MET | NM_001324402.2 | c.2520C>T | p.Gly840= | synonymous_variant | 19/20 | ||
MET | XM_011516223.2 | c.3867C>T | p.Gly1289= | synonymous_variant | 21/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.3810C>T | p.Gly1270= | synonymous_variant | 20/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.3864C>T | p.Gly1288= | synonymous_variant | 20/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*1415C>T | 3_prime_UTR_variant, NMD_transcript_variant | 19/20 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.000368 AC: 56AN: 152136Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000357 AC: 89AN: 249350Hom.: 0 AF XY: 0.000288 AC XY: 39AN XY: 135292
GnomAD4 exome AF: 0.000336 AC: 491AN: 1461622Hom.: 0 Cov.: 31 AF XY: 0.000340 AC XY: 247AN XY: 727136
GnomAD4 genome ? AF: 0.000368 AC: 56AN: 152254Hom.: 0 Cov.: 32 AF XY: 0.000269 AC XY: 20AN XY: 74452
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 29, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2022 | MET: BP4, BP7 - |
Hereditary cancer-predisposing syndrome Benign:2
Likely benign, criteria provided, single submitter | curation | Sema4, Sema4 | May 21, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2015 | 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 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Renal cell carcinoma Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Papillary renal cell carcinoma type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at