3-123690941-G-C

Position:

• chr3-123690941-G-C

Variant summary

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

The NM_053025.4(MYLK):​c.3565+1794C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 151,956 control chromosomes in the GnomAD database, including 27,094 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 0.53 (27094 hom., cov: 31)
• Consequence: MYLK NM_053025.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.215

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.758 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK	NM_053025.4	c.3565+1794C>G		intron_variant		ENST00000360304.8	NP_444253.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8	c.3565+1794C>G		intron_variant		5	NM_053025.4	ENSP00000353452.3

Frequencies

GnomAD3 genomes AF: 0.535 AC: 81170 AN: 151838 Hom.: 27097 Cov.: 31

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.534

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.0613

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.619

Gnomad MID AF: 0.699

Gnomad NFE AF: 0.764

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.534 AC: 81154 AN: 151956 Hom.: 27094 Cov.: 31 AF XY: 0.525 AC XY: 38962 AN XY: 74270

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.761

Gnomad4 EAS AF: 0.0612

Gnomad4 SAS AF: 0.468

Gnomad4 FIN AF: 0.619

Gnomad4 NFE AF: 0.764

Gnomad4 OTH AF: 0.567

Alfa AF: 0.632 Hom.: 4104

Bravo AF: 0.511

Asia WGS AF: 0.273 AC: 955 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	2.1
DANN	Benign	0.59

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: rs33264; hg19: chr3-123409788;