rs370499060
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The NM_000245.4(MET):c.146A>C(p.Glu49Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,728 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. 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. E49G) has been classified as Uncertain significance.
Frequency
Consequence
NM_000245.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.146A>C | p.Glu49Ala | missense_variant | 2/21 | ENST00000397752.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.146A>C | p.Glu49Ala | missense_variant | 2/21 | 1 | NM_000245.4 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249376Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135284
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461728Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727160
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 30, 2022 | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Intellectual disability Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille | Jan 01, 2019 | - - |
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 07, 2023 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 22, 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