rs777748634
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_000245.4(MET):c.3115G>A(p.Asp1039Asn) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,846 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D1039E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000245.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.3115G>A | p.Asp1039Asn | missense_variant | 15/21 | ENST00000397752.8 | |
MET | NM_001127500.3 | c.3169G>A | p.Asp1057Asn | missense_variant | 15/21 | ||
MET | NM_001324402.2 | c.1825G>A | p.Asp609Asn | missense_variant | 14/20 | ||
MET | XM_011516223.2 | c.3172G>A | p.Asp1058Asn | missense_variant | 16/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.3115G>A | p.Asp1039Asn | missense_variant | 15/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.3169G>A | p.Asp1057Asn | missense_variant | 15/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*720G>A | 3_prime_UTR_variant, NMD_transcript_variant | 14/20 | 1 | ||||
MET | ENST00000454623.1 | c.370G>A | p.Asp124Asn | missense_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249366Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135272
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461846Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727230
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1057 of the MET protein (p.Asp1057Asn). This variant is present in population databases (rs777748634, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with MET-related conditions. ClinVar contains an entry for this variant (Variation ID: 454233). 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. 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 12, 2024 | The p.D1057N variant (also known as c.3169G>A), located in coding exon 14 of the MET gene, results from a G to A substitution at nucleotide position 3169. The aspartic acid at codon 1057 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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