rs771328219
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_000245.4(MET):c.3118T>C(p.Ser1040Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000564 in 1,614,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1040C) has been classified as Uncertain significance.
Frequency
Consequence
NM_000245.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.3118T>C | p.Ser1040Pro | missense_variant | 15/21 | ENST00000397752.8 | |
MET | NM_001127500.3 | c.3172T>C | p.Ser1058Pro | missense_variant | 15/21 | ||
MET | NM_001324402.2 | c.1828T>C | p.Ser610Pro | missense_variant | 14/20 | ||
MET | XM_011516223.2 | c.3175T>C | p.Ser1059Pro | missense_variant | 16/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.3118T>C | p.Ser1040Pro | missense_variant | 15/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.3172T>C | p.Ser1058Pro | missense_variant | 15/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*723T>C | 3_prime_UTR_variant, NMD_transcript_variant | 14/20 | 1 | ||||
MET | ENST00000454623.1 | c.373T>C | p.Ser125Pro | missense_variant | 3/3 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000581 AC: 85AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.0000440 AC XY: 32AN XY: 727224
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74358
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 97 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jun 01, 2023 | - - |
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 1058 of the MET protein (p.Ser1058Pro). This variant is present in population databases (rs771328219, gnomAD 0.01%). 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: 246636). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 27, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in tumor and adjacent normal tissue from a patient with non-small cell lung cancer (PMID: 15735036); This variant is associated with the following publications: (PMID: 19037978, 19333071, 18340114, 23275061, 20139696, 31226345, 32964978, 15735036) - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 02, 2023 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at