rs11709947

Positions:

• chr3-123661934-C-T

Variant summary

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

The NM_053025.4(MYLK):​c.3985+2171G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.389 in 152,086 control chromosomes in the GnomAD database, including 14,754 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 0.39 (14754 hom., cov: 31)
• Consequence: MYLK NM_053025.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.805

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK	NM_053025.4	c.3985+2171G>A		intron_variant		ENST00000360304.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK	ENST00000360304.8	c.3985+2171G>A		intron_variant		5	NM_053025.4	P4

Frequencies

GnomAD3 genomes AF: 0.390 AC: 59209 AN: 151968 Hom.: 14765 Cov.: 31

Gnomad AFR AF: 0.109

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.528

Gnomad EAS AF: 0.0363

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.608

Gnomad MID AF: 0.427

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.409

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.389 AC: 59184 AN: 152086 Hom.: 14754 Cov.: 31 AF XY: 0.389 AC XY: 28924 AN XY: 74334

Gnomad4 AFR AF: 0.109

Gnomad4 AMR AF: 0.378

Gnomad4 ASJ AF: 0.528

Gnomad4 EAS AF: 0.0366

Gnomad4 SAS AF: 0.367

Gnomad4 FIN AF: 0.608

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.405

Alfa AF: 0.514 Hom.: 28358

Bravo AF: 0.360

Asia WGS AF: 0.185 AC: 648 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.46
DANN	Benign	0.53

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: rs11709947; hg19: chr3-123380781; COSMIC: COSV60607157; COSMIC: COSV60607157;