rs1343700

Variant names:

• chr3-123852907-G-A
• rs1343700
• NM_053025.4:c.-126-21237C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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 Gene-Disease associations (from GenCC):

• aortic aneurysm, familial thoracic 7

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• familial thoracic aortic aneurysm and aortic dissection

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, ClinGen
• megacystis-microcolon-intestinal hypoperistalsis syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: G2P
• connective tissue disorder

  Inheritance: AD Classification: MODERATE Submitted by: Genomics England PanelApp
• megacystis-microcolon-intestinal hypoperistalsis syndrome

  Inheritance: AD, AR Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYLK	NM_053025.4	c.-126-21237C>T		intron_variant	Intron 2 of 33	ENST00000360304.8	NP_444253.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8	c.-126-21237C>T		intron_variant	Intron 2 of 33	5	NM_053025.4	ENSP00000353452.3
MYLK	ENST00000464489.5	n.-126-21237C>T		intron_variant	Intron 2 of 32	1		ENSP00000417798.1
MYLK	ENST00000360772.7	c.-194-16972C>T		intron_variant	Intron 2 of 33	5		ENSP00000354004.3
MYLK	ENST00000693689.1	c.-126-21237C>T		intron_variant	Intron 2 of 32			ENSP00000510503.1

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

African (AFR) AF: 0.205 AC: 8490 AN: 41482

American (AMR) AF: 0.386 AC: 5881 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.592 AC: 2054 AN: 3468

East Asian (EAS) AF: 0.0327 AC: 169 AN: 5176

South Asian (SAS) AF: 0.370 AC: 1773 AN: 4794

European-Finnish (FIN) AF: 0.518 AC: 5462 AN: 10540

Middle Eastern (MID) AF: 0.500 AC: 147 AN: 294

European-Non Finnish (NFE) AF: 0.633 AC: 43007 AN: 67942

Other (OTH) AF: 0.470 AC: 992 AN: 2110

Alfa AF: 0.577 Hom.: 13447

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
PhyloP100		-1.5
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: rs1343700; hg19: chr3-123571754;