7-116778791-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM1BP4_Moderate
The NM_000245.4(MET):āc.3356G>Cā(p.Gly1119Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000719 in 1,613,964 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000245.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.3356G>C | p.Gly1119Ala | missense_variant | 17/21 | ENST00000397752.8 | NP_000236.2 | |
MET | NM_001127500.3 | c.3410G>C | p.Gly1137Ala | missense_variant | 17/21 | NP_001120972.1 | ||
MET | NM_001324402.2 | c.2066G>C | p.Gly689Ala | missense_variant | 16/20 | NP_001311331.1 | ||
MET | XM_011516223.2 | c.3413G>C | p.Gly1138Ala | missense_variant | 18/22 | XP_011514525.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.3356G>C | p.Gly1119Ala | missense_variant | 17/21 | 1 | NM_000245.4 | ENSP00000380860.3 | ||
MET | ENST00000318493.11 | c.3410G>C | p.Gly1137Ala | missense_variant | 17/21 | 1 | ENSP00000317272.6 | |||
MET | ENST00000436117.3 | n.*961G>C | non_coding_transcript_exon_variant | 16/20 | 1 | ENSP00000410980.2 | ||||
MET | ENST00000436117.3 | n.*961G>C | 3_prime_UTR_variant | 16/20 | 1 | ENSP00000410980.2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000442 AC: 11AN: 249146Hom.: 0 AF XY: 0.0000592 AC XY: 8AN XY: 135152
GnomAD4 exome AF: 0.0000759 AC: 111AN: 1461680Hom.: 0 Cov.: 31 AF XY: 0.0000688 AC XY: 50AN XY: 727156
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152284Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74472
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, no assertion criteria provided | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jul 13, 2012 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 26, 2023 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast or colorectal cancer (PMID: 29684080, 35264596); This variant is associated with the following publications: (PMID: 21774103, 22703879, 29684080, 35264596) - |
Autosomal recessive nonsyndromic hearing loss 97 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 25, 2024 | - - |
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 20, 2024 | This sequence change replaces glycine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1137 of the MET protein (p.Gly1137Ala). This variant is present in population databases (rs201037977, gnomAD 0.009%). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 41625). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MET protein function with a negative predictive value of 80%. 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. - |
Papillary renal cell carcinoma type 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Mendelics | Jul 02, 2018 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 29, 2018 | 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