rs1477354447
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_000245.4(MET):c.3633-4G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,924 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_000245.4 splice_region, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MET | NM_000245.4 | c.3633-4G>A | splice_region_variant, intron_variant | ENST00000397752.8 | NP_000236.2 | |||
MET | NM_001127500.3 | c.3687-4G>A | splice_region_variant, intron_variant | NP_001120972.1 | ||||
MET | NM_001324402.2 | c.2343-4G>A | splice_region_variant, intron_variant | NP_001311331.1 | ||||
MET | XM_011516223.2 | c.3690-4G>A | splice_region_variant, intron_variant | XP_011514525.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MET | ENST00000397752.8 | c.3633-4G>A | splice_region_variant, intron_variant | 1 | NM_000245.4 | ENSP00000380860.3 | ||||
MET | ENST00000318493.11 | c.3687-4G>A | splice_region_variant, intron_variant | 1 | ENSP00000317272.6 | |||||
MET | ENST00000436117.3 | n.*1238-4G>A | splice_region_variant, intron_variant | 1 | ENSP00000410980.2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461770Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727186
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152154Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74320
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 09, 2018 | The c.3687-4G>A intronic variant results from a G to A substitution 4 nucleotides upstream from coding exon 18 in the MET gene. This nucleotide position is poorly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is not predicted to have any significant effect on this splice acceptor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Renal cell carcinoma Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 26, 2019 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at