rs75967604

Positions:

chr3-123700269-GTTC-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PM4_SupportingBP6_Very_StrongBA1

The NM_053025.4(MYLK):c.3196_3198del(p.Glu1066del) variant causes a 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 inframe_deletion

Scores

Not classified

Clinical Significance

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

Conservation

PhyloP100: 1.76

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:

LOC105369194 (HGNC:):

LOC105369194 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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. Variant chr3-123700269-GTTC-G is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
MYLK	NM_053025.4 linkuse as main transcript	c.3196_3198del	p.Glu1066del	inframe_deletion	18/34	ENST00000360304.8	NP_444253.3
LOC105369194	XR_924417.4 linkuse as main transcript	n.108-3591_108-3589del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8 linkuse as main transcript	c.3196_3198del	p.Glu1066del	inframe_deletion	18/34	5	NM_053025.4	ENSP00000353452	P4	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

GnomAD3 exomes

AF:

0.0673

AC:

16931

AN:

251436

Hom.:

2812

AF XY:

0.0697

AC XY:

9472

AN XY:

135882

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 SAS exome

AF:

0.149

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

Gnomad4 AFR exome

AF:

0.0221

Gnomad4 AMR exome

AF:

0.0187

Gnomad4 ASJ exome

AF:

0.0112

Gnomad4 EAS exome

AF:

0.441

Gnomad4 SAS exome

AF:

0.146

Gnomad4 FIN exome

AF:

0.0180

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.0547

GnomAD4 genome

AF:

0.0370

AC:

5631

AN:

151992

Hom.:

713

Cov.:

AF XY:

0.0408

AC XY:

3030

AN XY:

74292

show subpopulations

Gnomad4 AFR

AF:

0.0243

Gnomad4 AMR

AF:

0.0189

Gnomad4 ASJ

AF:

0.0127

Gnomad4 EAS

AF:

0.477

Gnomad4 SAS

AF:

0.169

Gnomad4 FIN

AF:

0.0165

Gnomad4 NFE

AF:

0.0116

Gnomad4 OTH

AF:

0.0398

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

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jun 04, 2015	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). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 20, 2015	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Aug 18, 2020	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 27, 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. -

Familial thoracic aortic aneurysm and aortic dissection

Benign:3

Benign, criteria provided, single submitter	clinical testing	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	Apr 12, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Feb 19, 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. -
Likely benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Aortic aneurysm, familial thoracic 7

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over