rs768188910
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM1BP4_ModerateBP6
The NM_000245.4(MET):c.4034T>C(p.Ile1345Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000297 in 1,614,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. I1345I) has been classified as Likely benign.
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.4034T>C | p.Ile1345Thr | missense_variant | 21/21 | ENST00000397752.8 | |
MET | NM_001127500.3 | c.4088T>C | p.Ile1363Thr | missense_variant | 21/21 | ||
MET | NM_001324402.2 | c.2744T>C | p.Ile915Thr | missense_variant | 20/20 | ||
MET | XM_011516223.2 | c.4091T>C | p.Ile1364Thr | missense_variant | 22/22 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.4034T>C | p.Ile1345Thr | missense_variant | 21/21 | 1 | NM_000245.4 | P3 | |
MET | ENST00000318493.11 | c.4088T>C | p.Ile1363Thr | missense_variant | 21/21 | 1 | A2 | ||
MET | ENST00000436117.3 | c.*1639T>C | 3_prime_UTR_variant, NMD_transcript_variant | 20/20 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 249326Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135252
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461844Hom.: 0 Cov.: 57 AF XY: 0.0000330 AC XY: 24AN XY: 727232
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152168Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74338
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Aug 15, 2023 | - - |
Autosomal recessive nonsyndromic hearing loss 97 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Oct 18, 2023 | - - |
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 | Oct 31, 2018 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 21, 2022 | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function - |
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
Hereditary cancer-predisposing syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2023 | This alteration is classified as 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