3-123659687-C-G

Variant names:

• chr3-123659687-C-G
• rs39639
• NM_053025.4:c.3986-2259G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.496
• Publications: 7 publications found

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

LOC124909421 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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	c.3986-2259G>C		intron_variant	Intron 23 of 33	ENST00000360304.8	NP_444253.3

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.694 AC: 105503 AN: 151944 Hom.: 41932 Cov.: 31

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

GnomAD2 exomes AF: 0.748 AC: 169920 AN: 227072 AF XY: 0.767

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 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.: 0 AF XY: 0.801 AC XY: 167540 AN XY: 209218

African (AFR) AF: 0.311 AC: 3253 AN: 10448

American (AMR) AF: 0.565 AC: 20342 AN: 36006

Ashkenazi Jewish (ASJ) AF: 0.824 AC: 9640 AN: 11700

East Asian (EAS) AF: 0.374 AC: 4899 AN: 13108

South Asian (SAS) AF: 0.716 AC: 47414 AN: 66232

European-Finnish (FIN) AF: 0.902 AC: 15173 AN: 16826

Middle Eastern (MID) AF: 0.799 AC: 2264 AN: 2834

European-Non Finnish (NFE) AF: 0.913 AC: 174582 AN: 191318

Other (OTH) AF: 0.817 AC: 13512 AN: 16534

GnomAD4 genome AF: 0.694 AC: 105508 AN: 152062 Hom.: 41917 Cov.: 31 AF XY: 0.693 AC XY: 51524 AN XY: 74346

African (AFR) AF: 0.314 AC: 13006 AN: 41400

American (AMR) AF: 0.666 AC: 10171 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2847 AN: 3470

East Asian (EAS) AF: 0.373 AC: 1921 AN: 5154

South Asian (SAS) AF: 0.681 AC: 3287 AN: 4824

European-Finnish (FIN) AF: 0.911 AC: 9666 AN: 10614

Middle Eastern (MID) AF: 0.772 AC: 227 AN: 294

European-Non Finnish (NFE) AF: 0.911 AC: 61969 AN: 68006

Other (OTH) AF: 0.732 AC: 1543 AN: 2108

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
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs39639; hg19: chr3-123378534; COSMIC: COSV60605416;