chr7-116796025-C-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000245.4(MET):c.4074C>A(p.Asn1358Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N1358N) has been classified as Likely benign.
Frequency
Consequence
NM_000245.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.4074C>A | p.Asn1358Lys | missense_variant | 21/21 | ENST00000397752.8 | |
MET | NM_001127500.3 | c.4128C>A | p.Asn1376Lys | missense_variant | 21/21 | ||
MET | NM_001324402.2 | c.2784C>A | p.Asn928Lys | missense_variant | 20/20 | ||
MET | XM_011516223.2 | c.4131C>A | p.Asn1377Lys | missense_variant | 22/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.4074C>A | p.Asn1358Lys | missense_variant | 21/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.4128C>A | p.Asn1376Lys | missense_variant | 21/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*1679C>A | 3_prime_UTR_variant, NMD_transcript_variant | 20/20 | 1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461728Hom.: 0 Cov.: 57 AF XY: 0.00 AC XY: 0AN XY: 727176
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Renal cell carcinoma Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 14, 2023 | 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. 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 expected to disrupt MET protein function. This variant has not been reported in the literature in individuals affected with MET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces asparagine, which is neutral and polar, with lysine, which is basic and polar, at codon 1376 of the MET protein (p.Asn1376Lys). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.