rs820329

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_053025.4(MYLK):c.1651+6T>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.208 in 1,613,104 control chromosomes in the GnomAD database, including 38,752 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2636 hom., cov: 33)

Exomes 𝑓: 0.21 ( 36116 hom. )

Consequence

MYLK
NM_053025.4 splice_region, intron

Scores

Splicing: ADA: 0.3909

Clinical Significance

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

Conservation

PhyloP100: -0.152

Publications

8 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 Gene-Disease associations (from GenCC):

aortic aneurysm, familial thoracic 7
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
megacystis-microcolon-intestinal hypoperistalsis syndrome 1
Inheritance: AR Classification: STRONG Submitted by: G2P
familial thoracic aortic aneurysm and aortic dissection
Inheritance: Unknown, AD Classification: STRONG, SUPPORTIVE Submitted by: ClinGen, Orphanet
connective tissue disorder
Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
megacystis-microcolon-intestinal hypoperistalsis syndrome
Inheritance: AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

MYLK links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 3-123725938-A-T is Benign according to our data. Variant chr3-123725938-A-T is described in ClinVar as Benign. ClinVar VariationId is 226756.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053025.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
MYLK	NM_053025.4	MANE Select	c.1651+6T>A	splice_region intron	N/A	NP_444253.3
MYLK	NM_053027.4		c.1651+6T>A	splice_region intron	N/A	NP_444255.3
MYLK	NM_053026.4		c.1444+6T>A	splice_region intron	N/A	NP_444254.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYLK	ENST00000360304.8	TSL:5 MANE Select	c.1651+6T>A	splice_region intron	N/A	ENSP00000353452.3	Q15746-1
MYLK	ENST00000464489.5	TSL:1	n.*1230+6T>A	splice_region intron	N/A	ENSP00000417798.1	F8WBL7
MYLK	ENST00000687848.1		c.1681+6T>A	splice_region intron	N/A	ENSP00000508761.1	A0A8I5KU53

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

25194

AN:

152112

Hom.:

2637

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0631

Gnomad AMI

AF:

0.201

Gnomad AMR

AF:

0.148

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.00580

Gnomad SAS

AF:

0.0713

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.239

Gnomad OTH

AF:

0.193

GnomAD2 exomes

AF:

0.164

AC:

41102

AN:

249904

AF XY:

0.167

show subpopulations

Gnomad AFR exome

AF:

0.0608

Gnomad AMR exome

AF:

0.0968

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.00419

Gnomad FIN exome

AF:

0.234

Gnomad NFE exome

AF:

0.234

Gnomad OTH exome

AF:

0.192

GnomAD4 exome

AF:

0.212

AC:

309780

AN:

1460874

Hom.:

36116

Cov.:

AF XY:

0.209

AC XY:

151628

AN XY:

726606

show subpopulations

African (AFR)

AF:

0.0567

AC:

1896

AN:

33464

American (AMR)

AF:

0.102

AC:

4558

AN:

44658

Ashkenazi Jewish (ASJ)

AF:

0.176

AC:

4597

AN:

26110

East Asian (EAS)

AF:

0.00375

AC:

149

AN:

39686

South Asian (SAS)

AF:

0.0779

AC:

6712

AN:

86174

European-Finnish (FIN)

AF:

0.239

AC:

12736

AN:

53376

Middle Eastern (MID)

AF:

0.111

AC:

640

AN:

5766

European-Non Finnish (NFE)

AF:

0.240

AC:

266821

AN:

1111296

Other (OTH)

AF:

0.193

AC:

11671

AN:

60344

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

12769

25539

38308

51078

63847

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8768

17536

26304

35072

43840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.166

AC:

25200

AN:

152230

Hom.:

2636

Cov.:

AF XY:

0.161

AC XY:

11995

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0630

AC:

2617

AN:

41564

American (AMR)

AF:

0.148

AC:

2257

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.184

AC:

639

AN:

3468

East Asian (EAS)

AF:

0.00600

AC:

AN:

5164

South Asian (SAS)

AF:

0.0728

AC:

352

AN:

4834

European-Finnish (FIN)

AF:

0.227

AC:

2403

AN:

10602

Middle Eastern (MID)

AF:

0.126

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.239

AC:

16277

AN:

67984

Other (OTH)

AF:

0.191

AC:

404

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1064

2128

3192

4256

5320

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.186

Hom.:

986

Bravo

AF:

0.156

Asia WGS

AF:

0.0500

AC:

176

AN:

3478

EpiCase

AF:

0.225

EpiControl

AF:

0.226

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (7)

Aortic aneurysm, familial thoracic 7 (2)

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-0.15

Mutation Taster

=97/3

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.39

dbscSNV1_RF

Benign

0.52

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over