rs375353223
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS1
The NM_000245.4(MET):c.103A>T(p.Met35Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000607 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 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. M35I) 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.103A>T | p.Met35Leu | missense_variant | 2/21 | ENST00000397752.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.103A>T | p.Met35Leu | missense_variant | 2/21 | 1 | NM_000245.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000368 AC: 56AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000108 AC: 27AN: 249394Hom.: 0 AF XY: 0.0000739 AC XY: 10AN XY: 135294
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461698Hom.: 0 Cov.: 31 AF XY: 0.0000193 AC XY: 14AN XY: 727148
GnomAD4 genome ? AF: 0.000368 AC: 56AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.000376 AC XY: 28AN XY: 74436
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 19, 2020 | 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. - |
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | May 30, 2021 | - - |
Osteofibrous dysplasia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Jul 09, 2019 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 25, 2023 | See Variant Classification Assertion Criteria. - |
Hereditary cancer Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | Jan 23, 2024 | - - |
not specified Other:1
not provided, no classification provided | reference population | ITMI | Sep 19, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at