NM_000245.4:c.960G>T
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_StrongBP7
The NM_000245.4(MET):c.960G>T(p.Ala320Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000342 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A320A) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
MET
NM_000245.4 synonymous
NM_000245.4 synonymous
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -3.10
Publications
0 publications found
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]
COMETT (HGNC:51196): (cytosolic oncogenic antisense to MET transcript) This gene encodes a natural antisense transcript highly expressed in papillary thyroid carcinomas harboring BRAF V600E mutation or RET gene rearrangements. This lncRNA induces the downstream MAPK pathway and is part of a co-expression network including different oncogenes belonging to the MAPK and PI3H/AKT pathways. In thyroid carcinomas, this gene has oncogenic properties associated with increased proliferation and drug resistance. [provided by RefSeq, Jan 2020]
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ACMG classification
Classification was made for transcript
Our verdict: Likely_benign. The variant received -3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP7
Synonymous conserved (PhyloP=-3.1 with no splicing effect.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_000245.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MET | NM_000245.4 | MANE Select | c.960G>T | p.Ala320Ala | synonymous | Exon 2 of 21 | NP_000236.2 | ||
| MET | NM_001127500.3 | c.960G>T | p.Ala320Ala | synonymous | Exon 2 of 21 | NP_001120972.1 | |||
| MET | NM_001324401.3 | c.960G>T | p.Ala320Ala | synonymous | Exon 2 of 12 | NP_001311330.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MET | ENST00000397752.8 | TSL:1 MANE Select | c.960G>T | p.Ala320Ala | synonymous | Exon 2 of 21 | ENSP00000380860.3 | ||
| MET | ENST00000318493.11 | TSL:1 | c.960G>T | p.Ala320Ala | synonymous | Exon 2 of 21 | ENSP00000317272.6 | ||
| MET | ENST00000436117.3 | TSL:1 | n.960G>T | non_coding_transcript_exon | Exon 2 of 20 | ENSP00000410980.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD2 exomes AF: 0.00000804 AC: 2AN: 248856 AF XY: 0.00000741 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
248856
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461624Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727120 show subpopulations
GnomAD4 exome
AF:
AC:
5
AN:
1461624
Hom.:
Cov.:
32
AF XY:
AC XY:
1
AN XY:
727120
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33442
American (AMR)
AF:
AC:
0
AN:
44668
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26126
East Asian (EAS)
AF:
AC:
1
AN:
39694
South Asian (SAS)
AF:
AC:
1
AN:
86226
European-Finnish (FIN)
AF:
AC:
0
AN:
53396
Middle Eastern (MID)
AF:
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111926
Other (OTH)
AF:
AC:
1
AN:
60380
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.465
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
GnomAD4 genome
Cov.:
32
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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