NM_053025.4:c.4842T>C

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_053025.4(MYLK):c.4842T>C(p.Asn1614Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,612,880 control chromosomes in the GnomAD database, including 30,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 6022 hom., cov: 32)

Exomes 𝑓: 0.13 ( 24188 hom. )

Consequence

MYLK
NM_053025.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 0.0920

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.52).

BP6

Variant 3-123638190-A-G is Benign according to our data. Variant chr3-123638190-A-G is described in ClinVar as [Benign]. Clinvar id is 226771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-123638190-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=0.092 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK	NM_053025.4 link	c.4842T>C	p.Asn1614Asn	synonymous_variant	Exon 29 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.4842T>C	p.Asn1614Asn	synonymous_variant	Exon 29 of 34	5	NM_053025.4	ENSP00000353452.3		Q15746-1

Frequencies

GnomAD3 genomes

AF:

0.224

AC:

34032

AN:

151920

Hom.:

5995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.418

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.298

Gnomad ASJ

AF:

0.140

Gnomad EAS

AF:

0.620

Gnomad SAS

AF:

0.316

Gnomad FIN

AF:

0.0691

Gnomad MID

AF:

0.182

Gnomad NFE

AF:

0.0852

Gnomad OTH

AF:

0.198

GnomAD3 exomes

AF:

0.220

AC:

55157

AN:

250898

Hom.:

9919

AF XY:

0.208

AC XY:

28188

AN XY:

135620

show subpopulations

Gnomad AFR exome

AF:

0.425

Gnomad AMR exome

AF:

0.417

Gnomad ASJ exome

AF:

0.134

Gnomad EAS exome

AF:

0.608

Gnomad SAS exome

AF:

0.285

Gnomad FIN exome

AF:

0.0804

Gnomad NFE exome

AF:

0.0873

Gnomad OTH exome

AF:

0.178

GnomAD4 exome

AF:

0.130

AC:

189516

AN:

1460842

Hom.:

24188

Cov.:

AF XY:

0.132

AC XY:

96137

AN XY:

726720

show subpopulations

Gnomad4 AFR exome

AF:

0.432

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.644

Gnomad4 SAS exome

AF:

0.282

Gnomad4 FIN exome

AF:

0.0787

Gnomad4 NFE exome

AF:

0.0798

Gnomad4 OTH exome

AF:

0.160

GnomAD4 genome

AF:

0.224

AC:

34128

AN:

152038

Hom.:

6022

Cov.:

AF XY:

0.228

AC XY:

16931

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.419

Gnomad4 AMR

AF:

0.299

Gnomad4 ASJ

AF:

0.140

Gnomad4 EAS

AF:

0.621

Gnomad4 SAS

AF:

0.317

Gnomad4 FIN

AF:

0.0691

Gnomad4 NFE

AF:

0.0852

Gnomad4 OTH

AF:

0.202

Alfa

AF:

0.121

Hom.:

2226

Bravo

AF:

0.252

Asia WGS

AF:

0.459

AC:

1593

AN:

3478

EpiCase

AF:

0.0895

EpiControl

AF:

0.0911

ClinVar

Significance: 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

- -

Sep 23, 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. -

Aug 09, 2019

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Apr 04, 2013

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Asn1614Asn in exon 29 of MYLK: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 40.8% (1798/4406) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs820463). -

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Aortic aneurysm, familial thoracic 7

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Familial thoracic aortic aneurysm and aortic dissection

Benign:1

Jan 23, 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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.053

DANN

Benign

0.55

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