Genetic Variant NM_053025.4:c.4317T>C (chr3-123649166-A-G) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_053025.4(MYLK):c.4317T>C(p.Asp1439Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,612,966 control chromosomes in the GnomAD database, including 33,826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 7412 hom., cov: 32)

Exomes 𝑓: 0.14 ( 26414 hom. )

Consequence

MYLK
NM_053025.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: 1.28

Publications

14 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:

LOC124909421 (HGNC:):

LOC124909421 links:

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

MYLK-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP6

Variant 3-123649166-A-G is Benign according to our data. Variant chr3-123649166-A-G is described in ClinVar as Benign. ClinVar VariationId is 226770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.28 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.612 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	HGVSp	Effect	Exon Rank	Protein
MYLK	NM_053025.4	MANE Select	c.4317T>C	p.Asp1439Asp	synonymous	Exon 25 of 34	NP_444253.3
MYLK	NM_053027.4		c.4317T>C	p.Asp1439Asp	synonymous	Exon 25 of 33	NP_444255.3
MYLK	NM_053026.4		c.4110T>C	p.Asp1370Asp	synonymous	Exon 24 of 33	NP_444254.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYLK	ENST00000360304.8	TSL:5 MANE Select	c.4317T>C	p.Asp1439Asp	synonymous	Exon 25 of 34	ENSP00000353452.3	Q15746-1
MYLK	ENST00000464489.5	TSL:1	n.*3896T>C		non_coding_transcript_exon	Exon 24 of 33	ENSP00000417798.1	F8WBL7
MYLK	ENST00000464489.5	TSL:1	n.*3896T>C		3_prime_UTR	Exon 24 of 33	ENSP00000417798.1	F8WBL7

Frequencies

GnomAD3 genomes

AF:

0.248

AC:

37588

AN:

151740

Hom.:

7370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.486

Gnomad AMI

AF:

0.0450

Gnomad AMR

AF:

0.307

Gnomad ASJ

AF:

0.173

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.318

Gnomad FIN

AF:

0.0896

Gnomad MID

AF:

0.187

Gnomad NFE

AF:

0.0887

Gnomad OTH

AF:

0.215

GnomAD2 exomes

AF:

0.232

AC:

58278

AN:

251196

AF XY:

0.218

show subpopulations

Gnomad AFR exome

AF:

0.495

Gnomad AMR exome

AF:

0.425

Gnomad ASJ exome

AF:

0.170

Gnomad EAS exome

AF:

0.617

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0905

Gnomad OTH exome

AF:

0.190

GnomAD4 exome

AF:

0.135

AC:

197547

AN:

1461108

Hom.:

26414

Cov.:

AF XY:

0.138

AC XY:

100021

AN XY:

726860

show subpopulations

African (AFR)

AF:

0.509

AC:

17022

AN:

33442

American (AMR)

AF:

0.410

AC:

18347

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.172

AC:

4506

AN:

26136

East Asian (EAS)

AF:

0.653

AC:

25939

AN:

39700

South Asian (SAS)

AF:

0.285

AC:

24557

AN:

86226

European-Finnish (FIN)

AF:

0.0971

AC:

5183

AN:

53396

Middle Eastern (MID)

AF:

0.203

AC:

1051

AN:

5182

European-Non Finnish (NFE)

AF:

0.0816

AC:

90693

AN:

1111982

Other (OTH)

AF:

0.170

AC:

10249

AN:

60320

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

9345

18690

28034

37379

46724

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3994

7988

11982

15976

19970

<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:

0.248

AC:

37707

AN:

151858

Hom.:

7412

Cov.:

AF XY:

0.253

AC XY:

18758

AN XY:

74212

show subpopulations

African (AFR)

AF:

0.487

AC:

20122

AN:

41360

American (AMR)

AF:

0.308

AC:

4696

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.173

AC:

600

AN:

3468

East Asian (EAS)

AF:

0.630

AC:

3226

AN:

5118

South Asian (SAS)

AF:

0.319

AC:

1529

AN:

4796

European-Finnish (FIN)

AF:

0.0896

AC:

948

AN:

10586

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0887

AC:

6025

AN:

67946

Other (OTH)

AF:

0.219

AC:

463

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1162

2325

3487

4650

5812

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.193

Hom.:

4096

Bravo

AF:

0.276

Asia WGS

AF:

0.466

AC:

1619

AN:

3478

EpiCase

AF:

0.0921

EpiControl

AF:

0.0948

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (9)

Aortic aneurysm, familial thoracic 7 (2)

Familial thoracic aortic aneurysm and aortic dissection (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

4.8

(source)

DANN

Benign

0.73

PhyloP100

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

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

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