dbSNP rs146112057: MYLK:c.422+14G>C (chr3-123739939-C-G) – 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.422+14G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000692 in 1,613,798 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0036 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00039 ( 1 hom. )

Consequence

MYLK
NM_053025.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -0.821

Publications

0 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=-0.82).

BP6

Variant 3-123739939-C-G is Benign according to our data. Variant chr3-123739939-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 262283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00363 (553/152348) while in subpopulation AFR AF = 0.0127 (528/41598). AF 95% confidence interval is 0.0118. There are 5 homozygotes in GnomAd4. There are 244 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 5 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	Effect	Exon Rank	Protein
MYLK	NM_053025.4	MANE Select	c.422+14G>C	intron	N/A	NP_444253.3
MYLK	NM_053027.4		c.422+14G>C	intron	N/A	NP_444255.3
MYLK	NM_053026.4		c.422+14G>C	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.422+14G>C	intron	N/A	ENSP00000353452.3	Q15746-1
MYLK	ENST00000464489.5	TSL:1	n.*1+14G>C	intron	N/A	ENSP00000417798.1	F8WBL7
MYLK	ENST00000687848.1		c.452+14G>C	intron	N/A	ENSP00000508761.1	A0A8I5KU53

Frequencies

GnomAD3 genomes

AF:

0.00364

AC:

554

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00104

AC:

262

AN:

251448

AF XY:

0.000773

show subpopulations

Gnomad AFR exome

AF:

0.0142

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000264

Gnomad OTH exome

AF:

0.000652

GnomAD4 exome

AF:

0.000386

AC:

564

AN:

1461450

Hom.:

Cov.:

AF XY:

0.000352

AC XY:

256

AN XY:

727016

show subpopulations

African (AFR)

AF:

0.0132

AC:

443

AN:

33458

American (AMR)

AF:

0.000872

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53404

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0000243

AC:

AN:

1111698

Other (OTH)

AF:

0.000812

AC:

AN:

60362

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

123

154

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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:

0.00363

AC:

553

AN:

152348

Hom.:

Cov.:

AF XY:

0.00327

AC XY:

244

AN XY:

74506

show subpopulations

African (AFR)

AF:

0.0127

AC:

528

AN:

41598

American (AMR)

AF:

0.00111

AC:

AN:

15304

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.000207

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

120

150

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.0000698

Hom.:

Bravo

AF:

0.00436

Asia WGS

AF:

0.000866

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 (3)

Aortic aneurysm, familial thoracic 7 (2)

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

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.93

(source)

DANN

Benign

0.66

PhyloP100

-0.82

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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