rs369758288
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBP6
The NM_000245.4(MET):c.2555T>A(p.Met852Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,944 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. M852T) 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 -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.2555T>A | p.Met852Lys | missense_variant | 11/21 | ENST00000397752.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.2555T>A | p.Met852Lys | missense_variant | 11/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.2609T>A | p.Met870Lys | missense_variant | 11/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*160T>A | 3_prime_UTR_variant, NMD_transcript_variant | 10/20 | 1 | ||||
MET | ENST00000422097.2 | c.2555T>A | p.Met852Lys | missense_variant | 11/12 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152200Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248808Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134966
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1461626Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6AN XY: 727110
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152318Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74492
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
Papillary renal cell carcinoma type 1;C2239176:Hepatocellular carcinoma;C4084709:Autosomal recessive nonsyndromic hearing loss 97;C4085248:Osteofibrous dysplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Sep 30, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | May 19, 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 - |
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 02, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | May 11, 2022 | 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