rs12172926

Variant names:

• chr3-123700441-C-T
• rs12172926
• NM_053025.4:c.3027G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_053025.4(MYLK):​c.3027G>A​(p.Glu1009Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.038 in 1,609,724 control chromosomes in the GnomAD database, including 6,757 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (875 hom., cov: 30)
  • Exomes 𝑓: 0.036 (5882 hom.)
• Consequence: MYLK NM_053025.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 0.159
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-123700441-C-T is Benign according to our data. Variant chr3-123700441-C-T is described in ClinVar as Benign. ClinVar VariationId is 194902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.159 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.463 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.3027G>A	p.Glu1009Glu	synonymous	Exon 18 of 34	NP_444253.3
	MYLK	NM_053027.4		c.3027G>A	p.Glu1009Glu	synonymous	Exon 18 of 33	NP_444255.3
	MYLK	NM_053026.4		c.2820G>A	p.Glu940Glu	synonymous	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.3027G>A	p.Glu1009Glu	synonymous	Exon 18 of 34	ENSP00000353452.3	Q15746-1
	MYLK	ENST00000504946.6	TSL:1	c.636G>A	p.Glu212Glu	synonymous	Exon 2 of 4	ENSP00000510315.1	A0A8I5KYZ0
	MYLK	ENST00000464489.5	TSL:1	n.*2606G>A		non_coding_transcript_exon	Exon 17 of 33	ENSP00000417798.1	F8WBL7

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8187 AN: 151634 Hom.: 869 Cov.: 30

Gnomad AFR AF: 0.0821

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0268

Gnomad ASJ AF: 0.0133

Gnomad EAS AF: 0.479

Gnomad SAS AF: 0.180

Gnomad FIN AF: 0.0165

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0116

Gnomad OTH AF: 0.0476

GnomAD2 exomes AF: 0.0727 AC: 18166 AN: 249944 AF XY: 0.0741

Gnomad AFR exome AF: 0.0833

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.0123

Gnomad EAS exome AF: 0.506

Gnomad FIN exome AF: 0.0173

Gnomad NFE exome AF: 0.0109

Gnomad OTH exome AF: 0.0466

GnomAD4 exome AF: 0.0364 AC: 53006 AN: 1457972 Hom.: 5882 Cov.: 40 AF XY: 0.0394 AC XY: 28554 AN XY: 724660

African (AFR) AF: 0.0846 AC: 2811 AN: 33240

American (AMR) AF: 0.0215 AC: 954 AN: 44364

Ashkenazi Jewish (ASJ) AF: 0.0115 AC: 300 AN: 26024

East Asian (EAS) AF: 0.441 AC: 17474 AN: 39630

South Asian (SAS) AF: 0.156 AC: 13407 AN: 85968

European-Finnish (FIN) AF: 0.0179 AC: 957 AN: 53352

Middle Eastern (MID) AF: 0.0212 AC: 122 AN: 5748

European-Non Finnish (NFE) AF: 0.0121 AC: 13430 AN: 1109472

Other (OTH) AF: 0.0590 AC: 3551 AN: 60174

GnomAD4 genome AF: 0.0541 AC: 8215 AN: 151752 Hom.: 875 Cov.: 30 AF XY: 0.0574 AC XY: 4254 AN XY: 74160

African (AFR) AF: 0.0825 AC: 3410 AN: 41348

American (AMR) AF: 0.0266 AC: 406 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.0133 AC: 46 AN: 3470

East Asian (EAS) AF: 0.479 AC: 2416 AN: 5048

South Asian (SAS) AF: 0.180 AC: 864 AN: 4794

European-Finnish (FIN) AF: 0.0165 AC: 174 AN: 10572

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0116 AC: 786 AN: 67954

Other (OTH) AF: 0.0529 AC: 111 AN: 2100

Alfa AF: 0.0288 Hom.: 1264

Bravo AF: 0.0576

Asia WGS AF: 0.314 AC: 1089 AN: 3478

EpiCase AF: 0.0112

EpiControl AF: 0.0108

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	8	not specified (8)
-	-	2	Aortic aneurysm, familial thoracic 7 (2)
-	-	2	not provided (2)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.5
DANN	Benign	0.37
PhyloP100		0.16
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: rs12172926; hg19: chr3-123419288; COSMIC: COSV60609414; COSMIC: COSV60609414;