rs1343700

chr3-123852907-G-A

Variant summary

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

The NM_053025.4(MYLK):c.-126-21237C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.451 in 151,962 control chromosomes in the GnomAD database, including 18,488 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 0.45 (18488 hom., cov: 32)
• Consequence: MYLK NM_053025.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.55

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=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK	NM_053025.4	c.-126-21237C>T		intron_variant		ENST00000360304.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK	ENST00000360304.8	c.-126-21237C>T		intron_variant		5	NM_053025.4	P4
MYLK	ENST00000464489.5	c.-126-21237C>T		intron_variant, NMD_transcript_variant		1
MYLK	ENST00000360772.7	c.-194-16972C>T		intron_variant		5
MYLK	ENST00000693689.1	c.-126-21237C>T		intron_variant

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68486 AN: 151844 Hom.: 18486 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.570

Gnomad AMR AF: 0.386

Gnomad ASJ AF: 0.592

Gnomad EAS AF: 0.0330

Gnomad SAS AF: 0.368

Gnomad FIN AF: 0.518

Gnomad MID AF: 0.503

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.476

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

GnomAD4 genome AF: 0.451 AC: 68495 AN: 151962 Hom.: 18488 Cov.: 32 AF XY: 0.439 AC XY: 32620 AN XY: 74250

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.386

Gnomad4 ASJ AF: 0.592

Gnomad4 EAS AF: 0.0327

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.518

Gnomad4 NFE AF: 0.633

Gnomad4 OTH AF: 0.470

Alfa AF: 0.573 Hom.: 11942

Bravo AF: 0.428

Asia WGS AF: 0.176 AC: 614 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.71
Dann	Benign	0.69

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: rs1343700; hg19: chr3-123571754;