Genetic Variant MYLK:c.3986-2259G>C (chr3-123659687-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_053025.4(MYLK):c.3986-2259G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 517,068 control chromosomes in the GnomAD database, including 163,576 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.69 ( 41917 hom., cov: 31)

Exomes 𝑓: 0.80 ( 121659 hom. )

Consequence

MYLK
NM_053025.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.496

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.905 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK	NM_053025.4 link	c.3986-2259G>C		intron_variant	Intron 23 of 33	ENST00000360304.8	NP_444253.3	Q15746-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8 link	c.3986-2259G>C		intron_variant	Intron 23 of 33	5	NM_053025.4	ENSP00000353452.3		Q15746-1

Frequencies

GnomAD3 genomes

AF:

0.694

AC:

105503

AN:

151944

Hom.:

41932

Cov.:

show subpopulations

Gnomad AFR

AF:

0.314

Gnomad AMI

AF:

0.955

Gnomad AMR

AF:

0.666

Gnomad ASJ

AF:

0.820

Gnomad EAS

AF:

0.374

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.911

Gnomad MID

AF:

0.782

Gnomad NFE

AF:

0.911

Gnomad OTH

AF:

0.736

GnomAD3 exomes

AF:

0.748

AC:

169920

AN:

227072

Hom.:

68475

AF XY:

0.767

AC XY:

96258

AN XY:

125470

show subpopulations

Gnomad AFR exome

AF:

0.302

Gnomad AMR exome

AF:

0.564

Gnomad ASJ exome

AF:

0.827

Gnomad EAS exome

AF:

0.384

Gnomad SAS exome

AF:

0.713

Gnomad FIN exome

AF:

0.901

Gnomad NFE exome

AF:

0.909

Gnomad OTH exome

AF:

0.805

GnomAD4 exome

AF:

0.797

AC:

291079

AN:

365006

Hom.:

121659

Cov.:

AF XY:

0.801

AC XY:

167540

AN XY:

209218

show subpopulations

Gnomad4 AFR exome

AF:

0.311

Gnomad4 AMR exome

AF:

0.565

Gnomad4 ASJ exome

AF:

0.824

Gnomad4 EAS exome

AF:

0.374

Gnomad4 SAS exome

AF:

0.716

Gnomad4 FIN exome

AF:

0.902

Gnomad4 NFE exome

AF:

0.913

Gnomad4 OTH exome

AF:

0.817

GnomAD4 genome

AF:

0.694

AC:

105508

AN:

152062

Hom.:

41917

Cov.:

AF XY:

0.693

AC XY:

51524

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.314

Gnomad4 AMR

AF:

0.666

Gnomad4 ASJ

AF:

0.820

Gnomad4 EAS

AF:

0.373

Gnomad4 SAS

AF:

0.681

Gnomad4 FIN

AF:

0.911

Gnomad4 NFE

AF:

0.911

Gnomad4 OTH

AF:

0.732

Alfa

AF:

0.812

Hom.:

9710

Bravo

AF:

0.658

Asia WGS

AF:

0.527

AC:

1835

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.89

DANN

Benign

0.63

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over