7-116758466-A-G
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_000245.4(MET):c.2110A>G(p.Asn704Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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. N704S) has been classified as Likely benign.
Frequency
Consequence
NM_000245.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.2110A>G | p.Asn704Asp | missense_variant | 9/21 | ENST00000397752.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.2110A>G | p.Asn704Asp | missense_variant | 9/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.2110A>G | p.Asn704Asp | missense_variant | 9/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.2110A>G | p.Asn704Asp | missense_variant, NMD_transcript_variant | 9/20 | 1 | |||
MET | ENST00000422097.2 | c.2110A>G | p.Asn704Asp | missense_variant | 9/12 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000920 AC: 14AN: 152206Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 249194Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135210
GnomAD4 exome AF: 0.00000890 AC: 13AN: 1461398Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 727006
GnomAD4 genome ? AF: 0.0000920 AC: 14AN: 152206Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7AN XY: 74350
ClinVar
Submissions by phenotype
MET-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Sep 03, 2023 | The MET c.2110A>G variant is predicted to result in the amino acid substitution p.Asn704Asp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.029% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/7-116398520-A-G). In ClinVar, this variant has conflicting interpretations ranging from likely benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/219460/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 05, 2023 | 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; In silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown - |
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 22, 2019 | 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