rs201806277
Positions:
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP6_Moderate
The NM_053025.4(MYLK):c.2305G>A(p.Glu769Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000396 in 1,614,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000036 ( 0 hom. )
Consequence
MYLK
NM_053025.4 missense
NM_053025.4 missense
Scores
3
6
8
Clinical Significance
Conservation
PhyloP100: 6.93
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MYLK
BP6
?
Variant 3-123707839-C-T is Benign according to our data. Variant chr3-123707839-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 575277.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYLK | NM_053025.4 | c.2305G>A | p.Glu769Lys | missense_variant | 16/34 | ENST00000360304.8 | |
LOC105369194 | XR_924417.4 | n.251+3830C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK | ENST00000360304.8 | c.2305G>A | p.Glu769Lys | missense_variant | 16/34 | 5 | NM_053025.4 | P4 | |
ENST00000685586.1 | n.611+3830C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152216Hom.: 0 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
11
AN:
152216
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000139 AC: 35AN: 251466Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135912
GnomAD3 exomes
AF:
AC:
35
AN:
251466
Hom.:
AF XY:
AC XY:
21
AN XY:
135912
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000363 AC: 53AN: 1461888Hom.: 0 Cov.: 32 AF XY: 0.0000440 AC XY: 32AN XY: 727246
GnomAD4 exome
AF:
AC:
53
AN:
1461888
Hom.:
Cov.:
32
AF XY:
AC XY:
32
AN XY:
727246
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152334Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74492
GnomAD4 genome
?
AF:
AC:
11
AN:
152334
Hom.:
Cov.:
33
AF XY:
AC XY:
6
AN XY:
74492
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
?
AF:
AC:
12
Asia WGS
AF:
AC:
3
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Aortic aneurysm, familial thoracic 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Oct 20, 2023 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;L;.;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;N;N
REVEL
Benign
Sift
Benign
T;T;T;T;D;T
Sift4G
Pathogenic
D;D;D;D;D;D
Polyphen
D;D;D;D;D;D
Vest4
MVP
MPC
0.18
ClinPred
T
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