rs1554398360
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The ENST00000397752.8(MET):āc.2888A>Gā(p.Asp963Gly) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,500 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
ENST00000397752.8 missense, splice_region
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.2888A>G | p.Asp963Gly | missense_variant, splice_region_variant | 14/21 | ENST00000397752.8 | NP_000236.2 | |
MET | NM_001127500.3 | c.2942A>G | p.Asp981Gly | missense_variant, splice_region_variant | 14/21 | NP_001120972.1 | ||
MET | NM_001324402.2 | c.1598A>G | p.Asp533Gly | missense_variant, splice_region_variant | 13/20 | NP_001311331.1 | ||
MET | XM_011516223.2 | c.2945A>G | p.Asp982Gly | missense_variant, splice_region_variant | 15/22 | XP_011514525.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.2888A>G | p.Asp963Gly | missense_variant, splice_region_variant | 14/21 | 1 | NM_000245.4 | ENSP00000380860 | P3 | |
MET | ENST00000318493.11 | c.2942A>G | p.Asp981Gly | missense_variant, splice_region_variant | 14/21 | 1 | ENSP00000317272 | A2 | ||
MET | ENST00000436117.3 | c.*493A>G | splice_region_variant, 3_prime_UTR_variant, NMD_transcript_variant | 13/20 | 1 | ENSP00000410980 | ||||
MET | ENST00000454623.1 | c.283+195A>G | intron_variant | 5 | ENSP00000398140 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461500Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727038
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 12, 2022 | The p.D981G variant (also known as c.2942A>G) is located in coding exon 13 of the MET gene. The aspartic acid at codon 981 is replaced by glycine, an amino acid with similar properties. This change occurs in the first base pair of coding exon 13. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 22, 2021 | - - |
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Apr 28, 2023 | An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 454227). This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 981 of the MET protein (p.Asp981Gly). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at