chr3-123620185-GGCTGGAGAA-G

Variant names:

• chr3-123620185-GGCTGGAGAA-G
• rs146990616
• NM_053025.4:c.5368+13_5368+21delTTCTCCAGC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BS1 BS2

The NM_053025.4(MYLK):​c.5368+13_5368+21delTTCTCCAGC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00653 in 1,603,516 control chromosomes in the GnomAD database, including 42 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (40 hom.)
• Consequence: MYLK NM_053025.4 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.23
• Publications: 0 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)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP6: Variant 3-123620185-GGCTGGAGAA-G is Benign according to our data. Variant chr3-123620185-GGCTGGAGAA-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 420653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00537 (817/152046) while in subpopulation NFE AF = 0.00865 (588/67990). AF 95% confidence interval is 0.00807. There are 2 homozygotes in GnomAd4. There are 378 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AD,Unknown,AR gene

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.5368+13_5368+21delTTCTCCAGC		intron	N/A	NP_444253.3
	MYLK	NM_053027.4		c.5215+13_5215+21delTTCTCCAGC		intron	N/A	NP_444255.3
	MYLK	NM_053026.4		c.5161+13_5161+21delTTCTCCAGC		intron	N/A	NP_444254.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK	ENST00000360304.8	TSL:5 MANE Select	c.5368+13_5368+21delTTCTCCAGC		intron	N/A	ENSP00000353452.3	Q15746-1
	MYLK	ENST00000418370.6	TSL:1	c.88+13_88+21delTTCTCCAGC		intron	N/A	ENSP00000428967.1	Q15746-8
	MYLK	ENST00000578202.2	TSL:1	c.88+13_88+21delTTCTCCAGC		intron	N/A	ENSP00000463691.2	A0A8J9G5A3

Frequencies

GnomAD3 genomes AF: 0.00538 AC: 817 AN: 151960 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00118

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00472

Gnomad ASJ AF: 0.00893

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00530

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.00865

Gnomad OTH AF: 0.00527

GnomAD2 exomes AF: 0.00511 AC: 1284 AN: 251332 AF XY: 0.00540

Gnomad AFR exome AF: 0.00105

Gnomad AMR exome AF: 0.00269

Gnomad ASJ exome AF: 0.00615

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00531

Gnomad NFE exome AF: 0.00794

Gnomad OTH exome AF: 0.00537

GnomAD4 exome AF: 0.00665 AC: 9649 AN: 1451470 Hom.: 40 AF XY: 0.00658 AC XY: 4759 AN XY: 722778

African (AFR) AF: 0.000632 AC: 21 AN: 33246

American (AMR) AF: 0.00280 AC: 125 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.00617 AC: 161 AN: 26082

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39638

South Asian (SAS) AF: 0.00252 AC: 217 AN: 86042

European-Finnish (FIN) AF: 0.00537 AC: 287 AN: 53408

Middle Eastern (MID) AF: 0.00104 AC: 6 AN: 5752

European-Non Finnish (NFE) AF: 0.00771 AC: 8501 AN: 1102530

Other (OTH) AF: 0.00549 AC: 330 AN: 60060

GnomAD4 genome AF: 0.00537 AC: 817 AN: 152046 Hom.: 2 Cov.: 32 AF XY: 0.00509 AC XY: 378 AN XY: 74316

African (AFR) AF: 0.00118 AC: 49 AN: 41462

American (AMR) AF: 0.00471 AC: 72 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00893 AC: 31 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5162

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4812

European-Finnish (FIN) AF: 0.00530 AC: 56 AN: 10558

Middle Eastern (MID) AF: 0.00342 AC: 1 AN: 292

European-Non Finnish (NFE) AF: 0.00865 AC: 588 AN: 67990

Other (OTH) AF: 0.00523 AC: 11 AN: 2104

Alfa AF: 0.00709 Hom.: 0

Bravo AF: 0.00469

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not specified (2)
-	-	1	Aortic aneurysm, familial thoracic 7 (1)
-	-	1	Connective tissue disorder (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs146990616; hg19: chr3-123339032;