chr3-123700066-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_053025.4(MYLK):c.3402C>A(p.Asn1134Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N1134N) has been classified as Benign.
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 29)
Failed GnomAD Quality Control
Consequence
MYLK
NM_053025.4 missense
NM_053025.4 missense
Scores
1
9
9
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 2.47
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 151924Hom.: 0 Cov.: 29 FAILED QC
GnomAD3 genomes
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GnomAD4 exome Cov.: 70
GnomAD4 exome
Cov.:
70
GnomAD4 genome 0.00 AC: 0AN: 151924Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0AN XY: 74220
GnomAD4 genome
Data not reliable, filtered out with message: AC0
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151924
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29
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74220
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ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Uncertain
.;.;.;D;.;D
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
.;D;D;D;.;.
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
M;.;M;M;.;M
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N;N;N
REVEL
Uncertain
Sift
Uncertain
D;.;D;D;D;D
Sift4G
Uncertain
D;D;D;D;D;D
Polyphen
D;D;D;P;D;P
Vest4
MutPred
Gain of methylation at N1134 (P = 0.0126);.;Gain of methylation at N1134 (P = 0.0126);Gain of methylation at N1134 (P = 0.0126);.;Gain of methylation at N1134 (P = 0.0126);
MVP
MPC
0.19
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at