rs75967604

Variant names:

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_053025.4(MYLK):c.3196_3198delGAA(p.Glu1066del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,613,884 control chromosomes in the GnomAD database, including 6,375 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.037 ( 713 hom., cov: 30)

Exomes 𝑓: 0.034 ( 5662 hom. )

Consequence

MYLK
NM_053025.4 conservative_inframe_deletion

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.76

Publications

7 publications found

Variant links:

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]

MYLK links:

MYLK-AS1 (HGNC:42440): (MYLK antisense RNA 1)

MYLK-AS1 links:

LOC105369194 (HGNC:):

LOC105369194 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_053025.4. Strenght limited to Supporting due to length of the change: 1aa.

BP6

Variant 3-123700269-GTTC-G is Benign according to our data. Variant chr3-123700269-GTTC-G is described in ClinVar as [Likely_benign]. Clinvar id is 194904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK	NM_053025.4 link	c.3196_3198delGAA	p.Glu1066del	conservative_inframe_deletion	Exon 18 of 34	ENST00000360304.8	NP_444253.3	Q15746-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8 link	c.3196_3198delGAA	p.Glu1066del	conservative_inframe_deletion	Exon 18 of 34	5	NM_053025.4	ENSP00000353452.3		Q15746-1

Frequencies

GnomAD3 genomes

AF:

0.0371

AC:

5631

AN:

151874

Hom.:

714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0190

Gnomad ASJ

AF:

0.0127

Gnomad EAS

AF:

0.478

Gnomad SAS

AF:

0.169

Gnomad FIN

AF:

0.0165

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0116

Gnomad OTH

AF:

0.0373

GnomAD2 exomes

AF:

0.0673

AC:

16931

AN:

251436

AF XY:

0.0697

show subpopulations

Gnomad AFR exome

AF:

0.0249

Gnomad AMR exome

AF:

0.0186

Gnomad ASJ exome

AF:

0.0118

Gnomad EAS exome

AF:

0.506

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0110

Gnomad OTH exome

AF:

0.0438

GnomAD4 exome

AF:

0.0342

AC:

50049

AN:

1461892

Hom.:

5662

AF XY:

0.0373

AC XY:

27101

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.0221

AC:

740

AN:

33480

American (AMR)

AF:

0.0187

AC:

836

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0112

AC:

292

AN:

26136

East Asian (EAS)

AF:

0.441

AC:

17495

AN:

39700

South Asian (SAS)

AF:

0.146

AC:

12598

AN:

86258

European-Finnish (FIN)

AF:

0.0180

AC:

961

AN:

53418

Middle Eastern (MID)

AF:

0.0106

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0124

AC:

13760

AN:

1112012

Other (OTH)

AF:

0.0547

AC:

3306

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

2995

5991

8986

11982

14977

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0370

AC:

5631

AN:

151992

Hom.:

713

Cov.:

AF XY:

0.0408

AC XY:

3030

AN XY:

74292

show subpopulations

African (AFR)

AF:

0.0243

AC:

1007

AN:

41468

American (AMR)

AF:

0.0189

AC:

289

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.0127

AC:

AN:

3470

East Asian (EAS)

AF:

0.477

AC:

2430

AN:

5090

South Asian (SAS)

AF:

0.169

AC:

811

AN:

4790

European-Finnish (FIN)

AF:

0.0165

AC:

174

AN:

10568

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0116

AC:

791

AN:

67994

Other (OTH)

AF:

0.0398

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

199

397

596

794

993

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0193

Hom.:

Bravo

AF:

0.0378

Asia WGS

AF:

0.300

AC:

1039

AN:

3478

EpiCase

AF:

0.0106

EpiControl

AF:

0.0107

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:7

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 20, 2015

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 18, 2020

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 27, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jun 04, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

p.Glu1066del in exon 18 of MYLK: This variant is not expected to have clinical s ignificance because it has been identified in 50.4% (4361/8650) of East Asian ch romosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute. org; dbSNP rs75967604). -

Familial thoracic aortic aneurysm and aortic dissection

Benign:3

Feb 19, 2015

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Apr 12, 2019

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aortic aneurysm, familial thoracic 7

Benign:1

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.8

Mutation Taster

=75/25

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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rs75967604

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over