dbSNP rs41301337: MYLK:c.4620-12G>A (chr3-123640516-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_053025.4(MYLK):c.4620-12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 1,613,558 control chromosomes in the GnomAD database, including 974 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 83 hom., cov: 31)

Exomes 𝑓: 0.032 ( 891 hom. )

Consequence

MYLK
NM_053025.4 intron

Scores

Splicing: ADA: 0.00001352

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -1.14

Publications

1 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:

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=-0.89).

BP6

Variant 3-123640516-C-T is Benign according to our data. Variant chr3-123640516-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0293 (4466/152278) while in subpopulation NFE AF = 0.0344 (2341/68014). AF 95% confidence interval is 0.0333. There are 83 homozygotes in GnomAd4. There are 2059 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 83 AD,Unknown,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	Effect	Exon Rank	Protein
MYLK	NM_053025.4	MANE Select	c.4620-12G>A	intron	N/A	NP_444253.3
MYLK	NM_053027.4		c.4620-12G>A	intron	N/A	NP_444255.3
MYLK	NM_053026.4		c.4413-12G>A	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.4620-12G>A	intron	N/A	ENSP00000353452.3	Q15746-1
MYLK	ENST00000464489.5	TSL:1	n.*4199-12G>A	intron	N/A	ENSP00000417798.1	F8WBL7
MYLK	ENST00000687848.1		c.4650-12G>A	intron	N/A	ENSP00000508761.1	A0A8I5KU53

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4462

AN:

152160

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0343

Gnomad AMI

AF:

0.0219

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.0170

Gnomad EAS

AF:

0.000580

Gnomad SAS

AF:

0.0110

Gnomad FIN

AF:

0.0285

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0344

Gnomad OTH

AF:

0.0234

GnomAD2 exomes

AF:

0.0240

AC:

6016

AN:

250630

AF XY:

0.0241

show subpopulations

Gnomad AFR exome

AF:

0.0346

Gnomad AMR exome

AF:

0.0111

Gnomad ASJ exome

AF:

0.0159

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.0270

Gnomad NFE exome

AF:

0.0336

Gnomad OTH exome

AF:

0.0229

GnomAD4 exome

AF:

0.0322

AC:

47125

AN:

1461280

Hom.:

891

Cov.:

AF XY:

0.0317

AC XY:

23069

AN XY:

726962

show subpopulations

African (AFR)

AF:

0.0356

AC:

1192

AN:

33456

American (AMR)

AF:

0.0113

AC:

504

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0164

AC:

429

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0124

AC:

1068

AN:

86232

European-Finnish (FIN)

AF:

0.0257

AC:

1370

AN:

53408

Middle Eastern (MID)

AF:

0.0118

AC:

AN:

5318

European-Non Finnish (NFE)

AF:

0.0367

AC:

40783

AN:

1111970

Other (OTH)

AF:

0.0284

AC:

1713

AN:

60336

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

2573

5146

7720

10293

12866

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1506

3012

4518

6024

7530

<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:

0.0293

AC:

4466

AN:

152278

Hom.:

Cov.:

AF XY:

0.0277

AC XY:

2059

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0343

AC:

1425

AN:

41574

American (AMR)

AF:

0.0137

AC:

209

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0170

AC:

AN:

3472

East Asian (EAS)

AF:

0.000581

AC:

AN:

5164

South Asian (SAS)

AF:

0.0114

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0285

AC:

302

AN:

10608

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0344

AC:

2341

AN:

68014

Other (OTH)

AF:

0.0232

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

211

422

632

843

1054

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

108

162

216

270

<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:

0.0313

Hom.:

Bravo

AF:

0.0291

Asia WGS

AF:

0.00549

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (6)

Aortic aneurysm, familial thoracic 7 (2)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.32

(source)

DANN

Benign

0.77

PhyloP100

-1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000014

dbscSNV1_RF

Benign

0.0

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