rs860224

Variant names:

• chr3-123618567-C-G
• rs860224
• ENST00000515434.1:c.*61G>C

Your query was ambiguous. Multiple possible variants found:

• chr3-123618567-C-G
• chr3-123618567-C-T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000515434.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK	NM_053025.4	MANE Select	c.5500+72G>C		intron	N/A	NP_444253.3
	MYLK	NM_053027.4		c.5347+72G>C		intron	N/A	NP_444255.3
	MYLK	NM_053026.4		c.5293+72G>C		intron	N/A	NP_444254.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK	ENST00000515434.1	TSL:1	c.*61G>C		3_prime_UTR	Exon 2 of 2	ENSP00000509521.1
	MYLK	ENST00000360304.8	TSL:5 MANE Select	c.5500+72G>C		intron	N/A	ENSP00000353452.3
	MYLK	ENST00000418370.6	TSL:1	c.220+72G>C		intron	N/A	ENSP00000428967.1

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

African (AFR) AF: 0.772 AC: 25577 AN: 33148

American (AMR) AF: 0.464 AC: 20672 AN: 44534

Ashkenazi Jewish (ASJ) AF: 0.274 AC: 7087 AN: 25860

East Asian (EAS) AF: 0.639 AC: 25190 AN: 39400

South Asian (SAS) AF: 0.324 AC: 27691 AN: 85466

European-Finnish (FIN) AF: 0.120 AC: 6282 AN: 52348

Middle Eastern (MID) AF: 0.309 AC: 1765 AN: 5710

European-Non Finnish (NFE) AF: 0.174 AC: 191425 AN: 1099926

Other (OTH) AF: 0.258 AC: 15381 AN: 59654

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

African (AFR) AF: 0.749 AC: 31078 AN: 41476

American (AMR) AF: 0.391 AC: 5975 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.272 AC: 944 AN: 3470

East Asian (EAS) AF: 0.622 AC: 3202 AN: 5144

South Asian (SAS) AF: 0.350 AC: 1690 AN: 4824

European-Finnish (FIN) AF: 0.112 AC: 1186 AN: 10578

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.175 AC: 11897 AN: 67972

Other (OTH) AF: 0.348 AC: 734 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.1
DANN	Benign	0.50
PhyloP100		0.45
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: rs860224; hg19: chr3-123337414; COSMIC: COSV60605022;