NM_053025.4:c.3196_3198delGAA

Variant names:

• chr3-123700269-GTTC-G
• rs75967604
• NM_053025.4:c.3196_3198delGAA

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 1P and 16B. PM4_Supporting BP6_Very_Strong BA1

The NM_053025.4(MYLK):​c.3196_3198delGAA​(p.Glu1066del) variant causes a conservative inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0345 in 1,613,884 control chromosomes in the GnomAD database, including 6,375 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.037 (713 hom., cov: 30)
  • Exomes 𝑓: 0.034 (5662 hom.)
• Consequence: MYLK NM_053025.4 conservative_inframe_deletion
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 1.76
• Publications: 7 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)

LOC105369194 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_053025.4. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 3-123700269-GTTC-G is Benign according to our data. Variant chr3-123700269-GTTC-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 194904.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.462 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053025.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK	NM_053025.4	MANE Select	c.3196_3198delGAA	p.Glu1066del	conservative_inframe_deletion	Exon 18 of 34	NP_444253.3
	MYLK	NM_053027.4		c.3196_3198delGAA	p.Glu1066del	conservative_inframe_deletion	Exon 18 of 33	NP_444255.3
	MYLK	NM_053026.4		c.2989_2991delGAA	p.Glu997del	conservative_inframe_deletion	Exon 17 of 33	NP_444254.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK	ENST00000360304.8	TSL:5 MANE Select	c.3196_3198delGAA	p.Glu1066del	conservative_inframe_deletion	Exon 18 of 34	ENSP00000353452.3	Q15746-1
	MYLK	ENST00000504946.6	TSL:1	c.805_807delGAA	p.Glu269del	conservative_inframe_deletion	Exon 2 of 4	ENSP00000510315.1	A0A8I5KYZ0
	MYLK	ENST00000464489.5	TSL:1	n.*2775_*2777delGAA		non_coding_transcript_exon	Exon 17 of 33	ENSP00000417798.1	F8WBL7

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5631 AN: 151874 Hom.: 714 Cov.: 30

Gnomad AFR AF: 0.0243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0373

GnomAD2 exomes AF: 0.0673 AC: 16931 AN: 251436 AF XY: 0.0697

Gnomad AFR exome AF: 0.0249

Gnomad AMR exome AF: 0.0186

Gnomad ASJ exome AF: 0.0118

Gnomad EAS exome AF: 0.506

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0110

Gnomad OTH exome AF: 0.0438

GnomAD4 exome AF: 0.0342 AC: 50049 AN: 1461892 Hom.: 5662 AF XY: 0.0373 AC XY: 27101 AN XY: 727246

African (AFR) AF: 0.0221 AC: 740 AN: 33480

American (AMR) AF: 0.0187 AC: 836 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0112 AC: 292 AN: 26136

East Asian (EAS) AF: 0.441 AC: 17495 AN: 39700

South Asian (SAS) AF: 0.146 AC: 12598 AN: 86258

European-Finnish (FIN) AF: 0.0180 AC: 961 AN: 53418

Middle Eastern (MID) AF: 0.0106 AC: 61 AN: 5768

European-Non Finnish (NFE) AF: 0.0124 AC: 13760 AN: 1112012

Other (OTH) AF: 0.0547 AC: 3306 AN: 60396

GnomAD4 genome AF: 0.0370 AC: 5631 AN: 151992 Hom.: 713 Cov.: 30 AF XY: 0.0408 AC XY: 3030 AN XY: 74292

African (AFR) AF: 0.0243 AC: 1007 AN: 41468

American (AMR) AF: 0.0189 AC: 289 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3470

East Asian (EAS) AF: 0.477 AC: 2430 AN: 5090

South Asian (SAS) AF: 0.169 AC: 811 AN: 4790

European-Finnish (FIN) AF: 0.0165 AC: 174 AN: 10568

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 791 AN: 67994

Other (OTH) AF: 0.0398 AC: 84 AN: 2112

Alfa AF: 0.0193 Hom.: 37

Bravo AF: 0.0378

Asia WGS AF: 0.300 AC: 1039 AN: 3478

EpiCase AF: 0.0106

EpiControl AF: 0.0107

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	3	Familial thoracic aortic aneurysm and aortic dissection (3)
-	-	1	Aortic aneurysm, familial thoracic 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.8
Mutation Taster		=75/25	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: rs75967604; hg19: chr3-123419116; COSMIC: COSV100658570; COSMIC: COSV100658570;