7-116771839-C-G
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The NM_000245.4(MET):c.2888-10C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: not found (cov: 32)
Consequence
MET
NM_000245.4 splice_polypyrimidine_tract, intron
NM_000245.4 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.9531
2
Clinical Significance
Conservation
PhyloP100: 0.590
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 Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.22).
BP6
Variant 7-116771839-C-G is Benign according to our data. Variant chr7-116771839-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 416942.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.2888-10C>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000397752.8 | NP_000236.2 | |||
MET | NM_001127500.3 | c.2942-10C>G | splice_polypyrimidine_tract_variant, intron_variant | NP_001120972.1 | ||||
MET | NM_001324402.2 | c.1598-10C>G | splice_polypyrimidine_tract_variant, intron_variant | NP_001311331.1 | ||||
MET | XM_011516223.2 | c.2945-10C>G | splice_polypyrimidine_tract_variant, intron_variant | XP_011514525.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.2888-10C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000245.4 | ENSP00000380860 | P3 | |||
MET | ENST00000318493.11 | c.2942-10C>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | ENSP00000317272 | A2 | ||||
MET | ENST00000436117.3 | c.*493-10C>G | splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant | 1 | ENSP00000410980 | |||||
MET | ENST00000454623.1 | c.283+185C>G | intron_variant | 5 | ENSP00000398140 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 32
GnomAD4 exome
Cov.:
32
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 10, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at