rs886229659
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_053025.4(MYLK):c.4459C>T(p.Arg1487Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★). Synonymous variant affecting the same amino acid position (i.e. R1487R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_053025.4 stop_gained
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYLK | NM_053025.4 | c.4459C>T | p.Arg1487Ter | stop_gained | 27/34 | ENST00000360304.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK | ENST00000360304.8 | c.4459C>T | p.Arg1487Ter | stop_gained | 27/34 | 5 | NM_053025.4 | P4 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251430Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135892
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461888Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727246
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Aortic aneurysm, familial thoracic 7 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 11, 2022 | This variant is present in population databases (no rsID available, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 268203). This premature translational stop signal has been observed in individual(s) with thoracic aortic aneurysm and dissection (PMID: 25907466, 28401540). This sequence change creates a premature translational stop signal (p.Arg1487*) in the MYLK gene. This variant occurs within the aortic-specific isoform of MYLK. Loss-of-function variants in the aortic-specific isoform of MYLK are known to be pathogenic for thoracic aortic dissections (PMID: 21055718). - |
Pathogenic, no assertion criteria provided | research | Cardiogenetics, Center of Medical Genetics, Antwerp, Belgium | Nov 03, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at