rs860224

chr3-123618567-C-Gchr3-123618567-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000515434.1(MYLK):c.*61G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 1,598,118 control chromosomes in the GnomAD database, including 64,271 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 0.37 (15711 hom., cov: 32)
  • Exomes 𝑓: 0.22 (48560 hom.)
• Consequence: MYLK ENST00000515434.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.453

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)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK	NM_053025.4	c.5500+72G>C		intron_variant		ENST00000360304.8
MYLK-AS1	NR_038266.2	n.290-10927C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK	ENST00000360304.8	c.5500+72G>C		intron_variant		5	NM_053025.4	P4
MYLK-AS1	ENST00000485162.5	n.261-10927C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.374 AC: 56776 AN: 151954 Hom.: 15654 Cov.: 32

Gnomad AFR AF: 0.749

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.390

Gnomad ASJ AF: 0.272

Gnomad EAS AF: 0.621

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.112

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.175

Gnomad OTH AF: 0.345

GnomAD4 exome AF: 0.222 AC: 321070 AN: 1446046 Hom.: 48560 Cov.: 26 AF XY: 0.222 AC XY: 159980 AN XY: 719864

Gnomad4 AFR exome AF: 0.772

Gnomad4 AMR exome AF: 0.464

Gnomad4 ASJ exome AF: 0.274

Gnomad4 EAS exome AF: 0.639

Gnomad4 SAS exome AF: 0.324

Gnomad4 FIN exome AF: 0.120

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.258

GnomAD4 genome AF: 0.374 AC: 56906 AN: 152072 Hom.: 15711 Cov.: 32 AF XY: 0.372 AC XY: 27623 AN XY: 74342

Gnomad4 AFR AF: 0.749

Gnomad4 AMR AF: 0.391

Gnomad4 ASJ AF: 0.272

Gnomad4 EAS AF: 0.622

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.112

Gnomad4 NFE AF: 0.175

Gnomad4 OTH AF: 0.348

Alfa AF: 0.0847 Hom.: 124

Bravo AF: 0.413

Asia WGS AF: 0.488 AC: 1700 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	5.1
Dann	Benign	0.50

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

Other links and lift over

dbSNP: rs860224; hg19: chr3-123337414; COSMIC: COSV60605022;