rs372238373
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000245.4(MET):c.3477C>G(p.Tyr1159*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. Y1159Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000245.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.3477C>G | p.Tyr1159* | stop_gained | 17/21 | ENST00000397752.8 | NP_000236.2 | |
MET | NM_001127500.3 | c.3531C>G | p.Tyr1177* | stop_gained | 17/21 | NP_001120972.1 | ||
MET | NM_001324402.2 | c.2187C>G | p.Tyr729* | stop_gained | 16/20 | NP_001311331.1 | ||
MET | XM_011516223.2 | c.3534C>G | p.Tyr1178* | stop_gained | 18/22 | XP_011514525.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.3477C>G | p.Tyr1159* | stop_gained | 17/21 | 1 | NM_000245.4 | ENSP00000380860.3 | ||
MET | ENST00000318493.11 | c.3531C>G | p.Tyr1177* | stop_gained | 17/21 | 1 | ENSP00000317272.6 | |||
MET | ENST00000436117.3 | n.*1082C>G | non_coding_transcript_exon_variant | 16/20 | 1 | ENSP00000410980.2 | ||||
MET | ENST00000436117.3 | n.*1082C>G | 3_prime_UTR_variant | 16/20 | 1 | ENSP00000410980.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 26, 2024 | Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is not a known mechanism of disease - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2022 | The p.Y1177* variant (also known as c.3531C>G), located in coding exon 16 of the MET gene, results from a C to G substitution at nucleotide position 3531. This changes the amino acid from a tyrosine to a stop codon within coding exon 16. This alteration is expected to result in premature protein truncation or nonsense-mediated mRNA decay. However, loss of function of MET has not been clearly established as a mechanism of disease. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.