Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_053025.4(MYLK):c.3075C>T(p.Pro1025Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000827 in 1,613,650 control chromosomes in the GnomAD database, including 19 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00086 ( 19 hom. )

Consequence

MYLK
NM_053025.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.148

Publications

5 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:

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

MYLK-AS1 links:

LOC105369194 (HGNC:):

LOC105369194 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=-0.83).

BP6

Variant 3-123700393-G-A is Benign according to our data. Variant chr3-123700393-G-A is described in ClinVar as Benign. ClinVar VariationId is 226760.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.148 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.00054 (82/151954) while in subpopulation SAS AF = 0.0113 (54/4796). AF 95% confidence interval is 0.00886. There are 0 homozygotes in GnomAd4. There are 49 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAdExome4 at 19 AD,AR gene

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.3075C>T	p.Pro1025Pro	synonymous	Exon 18 of 34	NP_444253.3
MYLK	NM_053027.4		c.3075C>T	p.Pro1025Pro	synonymous	Exon 18 of 33	NP_444255.3
MYLK	NM_053026.4		c.2868C>T	p.Pro956Pro	synonymous	Exon 17 of 33	NP_444254.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYLK	ENST00000360304.8	TSL:5 MANE Select	c.3075C>T	p.Pro1025Pro	synonymous	Exon 18 of 34	ENSP00000353452.3
MYLK	ENST00000504946.6	TSL:1	c.684C>T	p.Pro228Pro	synonymous	Exon 2 of 4	ENSP00000510315.1
MYLK	ENST00000464489.5	TSL:1	n.*2654C>T		non_coding_transcript_exon	Exon 17 of 33	ENSP00000417798.1

Frequencies

GnomAD3 genomes

AF:

0.000547

AC:

AN:

151836

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.0115

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00164

AC:

413

AN:

251398

AF XY:

0.00220

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.0000544

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000237

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.000857

AC:

1253

AN:

1461696

Hom.:

Cov.:

AF XY:

0.00119

AC XY:

866

AN XY:

727180

show subpopulations

African (AFR)

AF:

0.000180

AC:

AN:

33412

American (AMR)

AF:

0.000134

AC:

AN:

44670

Ashkenazi Jewish (ASJ)

AF:

0.000421

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0117

AC:

1006

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00451

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000119

AC:

132

AN:

1111964

Other (OTH)

AF:

0.00109

AC:

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

170

254

339

424

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.000540

AC:

AN:

151954

Hom.:

Cov.:

AF XY:

0.000660

AC XY:

AN XY:

74250

show subpopulations

African (AFR)

AF:

0.0000724

AC:

AN:

41416

American (AMR)

AF:

0.000131

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.000576

AC:

AN:

3470

East Asian (EAS)

AF:

0.000195

AC:

AN:

5122

South Asian (SAS)

AF:

0.0113

AC:

AN:

4796

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10576

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

67974

Other (OTH)

AF:

0.00143

AC:

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000202

Hom.:

Bravo

AF:

0.000253

Asia WGS

AF:

0.00144

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000533

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (4)

not provided (3)

Familial thoracic aortic aneurysm and aortic dissection (2)

Aortic aneurysm, familial thoracic 7 (1)

Aortic aneurysm, familial thoracic 7;C5542316:Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

3.1

(source)

DANN

Benign

0.42

PhyloP100

-0.15

Mutation Taster

=100/0

polymorphism

(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.

NM_053025.4:c.3075C>T

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

ClinVar submissions as Germline

Computational scores

Splicing

Publications

Other links and lift over