rs113035707
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2
The NM_053025.4(MYLK):c.652C>T(p.Leu218=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000742 in 1,614,218 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0041 ( 11 hom., cov: 32)
Exomes 𝑓: 0.00039 ( 8 hom. )
Consequence
MYLK
NM_053025.4 synonymous
NM_053025.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 1.25
Genes affected
MYLK (HGNC:7590): (myosin light chain kinase) This gene, a muscle member of the immunoglobulin gene superfamily, encodes myosin light chain kinase which is a calcium/calmodulin dependent enzyme. This kinase phosphorylates myosin regulatory light chains to facilitate myosin interaction with actin filaments to produce contractile activity. This gene encodes both smooth muscle and nonmuscle isoforms. In addition, using a separate promoter in an intron in the 3' region, it encodes telokin, a small protein identical in sequence to the C-terminus of myosin light chain kinase, that is independently expressed in smooth muscle and functions to stabilize unphosphorylated myosin filaments. A pseudogene is located on the p arm of chromosome 3. Four transcript variants that produce four isoforms of the calcium/calmodulin dependent enzyme have been identified as well as two transcripts that produce two isoforms of telokin. Additional variants have been identified but lack full length transcripts. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -19 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.36).
BP6
?
Variant 3-123737480-G-A is Benign according to our data. Variant chr3-123737480-G-A is described in ClinVar as [Benign]. Clinvar id is 262295.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-123737480-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=1.25 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0041 (625/152338) while in subpopulation AFR AF= 0.0146 (605/41574). AF 95% confidence interval is 0.0136. There are 11 homozygotes in gnomad4. There are 302 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd at 9 AD,AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYLK | NM_053025.4 | c.652C>T | p.Leu218= | synonymous_variant | 8/34 | ENST00000360304.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK | ENST00000360304.8 | c.652C>T | p.Leu218= | synonymous_variant | 8/34 | 5 | NM_053025.4 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.00400 AC: 609AN: 152220Hom.: 9 Cov.: 32
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GnomAD3 exomes AF: 0.00115 AC: 290AN: 251478Hom.: 4 AF XY: 0.000934 AC XY: 127AN XY: 135910
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GnomAD4 exome AF: 0.000392 AC: 573AN: 1461880Hom.: 8 Cov.: 32 AF XY: 0.000348 AC XY: 253AN XY: 727234
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ClinVar
Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 01, 2016 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Oct 15, 2019 | - - |
Familial thoracic aortic aneurysm and aortic dissection Benign:2
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 11, 2015 | 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. - |
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Sep 07, 2017 | - - |
Aortic aneurysm, familial thoracic 7 Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Apr 29, 2021 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at