rs1251215478
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Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6_Very_StrongBP7
The NM_000245.4(MET):c.3231T>A(p.Ile1077=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000743 in 1,614,056 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 (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000075 ( 0 hom. )
Consequence
MET
NM_000245.4 synonymous
NM_000245.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.349
Genes affected
MET (HGNC:7029): (MET proto-oncogene, receptor tyrosine kinase) This gene encodes a member of the receptor tyrosine kinase family of proteins and the product of the proto-oncogene MET. The encoded preproprotein is proteolytically processed to generate alpha and beta subunits that are linked via disulfide bonds to form the mature receptor. Further processing of the beta subunit results in the formation of the M10 peptide, which has been shown to reduce lung fibrosis. Binding of its ligand, hepatocyte growth factor, induces dimerization and activation of the receptor, which plays a role in cellular survival, embryogenesis, and cellular migration and invasion. Mutations in this gene are associated with papillary renal cell carcinoma, hepatocellular carcinoma, and various head and neck cancers. Amplification and overexpression of this gene are also associated with multiple human cancers. [provided by RefSeq, May 2016]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -11 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.34).
BP6
?
Variant 7-116775083-T-A is Benign according to our data. Variant chr7-116775083-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 524914.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.349 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.3231T>A | p.Ile1077= | synonymous_variant | 15/21 | ENST00000397752.8 | |
MET | NM_001127500.3 | c.3285T>A | p.Ile1095= | synonymous_variant | 15/21 | ||
MET | NM_001324402.2 | c.1941T>A | p.Ile647= | synonymous_variant | 14/20 | ||
MET | XM_011516223.2 | c.3288T>A | p.Ile1096= | synonymous_variant | 16/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.3231T>A | p.Ile1077= | synonymous_variant | 15/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.3285T>A | p.Ile1095= | synonymous_variant | 15/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*836T>A | 3_prime_UTR_variant, NMD_transcript_variant | 14/20 | 1 | ||||
MET | ENST00000454623.1 | downstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152216Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249492Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135348
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GnomAD4 exome AF: 0.00000752 AC: 11AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727228
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 14, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 01, 2018 | 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. - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at