rs144126521
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000245.4(MET):c.-14-4G>A variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000571 in 1,613,656 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_000245.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.-14-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000397752.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.-14-4G>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_000245.4 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00309 AC: 470AN: 152056Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.000794 AC: 198AN: 249278Hom.: 4 AF XY: 0.000614 AC XY: 83AN XY: 135252
GnomAD4 exome AF: 0.000308 AC: 450AN: 1461482Hom.: 4 Cov.: 31 AF XY: 0.000257 AC XY: 187AN XY: 727050
GnomAD4 genome ? AF: 0.00310 AC: 472AN: 152174Hom.: 4 Cov.: 32 AF XY: 0.00308 AC XY: 229AN XY: 74408
ClinVar
Submissions by phenotype
not specified Benign:5
Benign, criteria provided, single submitter | clinical testing | Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital | Feb 06, 2024 | - - |
Benign, no assertion criteria provided | clinical testing | Eurofins Ntd Llc (ga) | Jan 17, 2013 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Feb 18, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 03, 2021 | This variant is associated with the following publications: (PMID: 27028822) - |
Papillary renal cell carcinoma type 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at