rs820463

Variant names:

• chr3-123638190-A-G
• rs820463
• NM_053025.4:c.4842T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-123638190-A-G
• chr3-123638190-A-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.0920
• Publications: 21 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 226771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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	c.4842T>C	p.Asn1614Asn	synonymous_variant	Exon 29 of 34	ENST00000360304.8	NP_444253.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8	c.4842T>C	p.Asn1614Asn	synonymous_variant	Exon 29 of 34	5	NM_053025.4	ENSP00000353452.3

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34032 AN: 151920 Hom.: 5995 Cov.: 32

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

GnomAD2 exomes AF: 0.220 AC: 55157 AN: 250898 AF XY: 0.208

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 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.: 33 AF XY: 0.132 AC XY: 96137 AN XY: 726720

African (AFR) AF: 0.432 AC: 14434 AN: 33430

American (AMR) AF: 0.404 AC: 18011 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3584 AN: 26120

East Asian (EAS) AF: 0.644 AC: 25568 AN: 39678

South Asian (SAS) AF: 0.282 AC: 24292 AN: 86190

European-Finnish (FIN) AF: 0.0787 AC: 4202 AN: 53412

Middle Eastern (MID) AF: 0.184 AC: 1002 AN: 5442

European-Non Finnish (NFE) AF: 0.0798 AC: 88759 AN: 1111608

Other (OTH) AF: 0.160 AC: 9664 AN: 60326

GnomAD4 genome AF: 0.224 AC: 34128 AN: 152038 Hom.: 6022 Cov.: 32 AF XY: 0.228 AC XY: 16931 AN XY: 74316

African (AFR) AF: 0.419 AC: 17324 AN: 41390

American (AMR) AF: 0.299 AC: 4571 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3179 AN: 5120

South Asian (SAS) AF: 0.317 AC: 1528 AN: 4826

European-Finnish (FIN) AF: 0.0691 AC: 734 AN: 10620

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.0852 AC: 5791 AN: 68008

Other (OTH) AF: 0.202 AC: 428 AN: 2114

Alfa AF: 0.147 Hom.: 4469

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:12

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:8

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). -

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. -

-

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

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

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

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

- -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

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

- -

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
PhyloP100		0.092
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs820463; hg19: chr3-123357037; COSMIC: COSV60607062; COSMIC: COSV60607062;