rs753024354

Variant names:

• chr3-123614135-A-C
• rs753024354
• NM_053025.4:c.5715T>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_053025.4(MYLK):​c.5715T>G​(p.Gly1905Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,609,582 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.000061 (0 hom., cov: 31)
  • Exomes 𝑓: 0.00011 (0 hom.)
• Consequence: MYLK NM_053025.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.841
• Publications: 4 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-123614135-A-C is Benign according to our data. Variant chr3-123614135-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 511342.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.841 with no splicing effect.

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.5715T>G	p.Gly1905Gly	synonymous	Exon 34 of 34	NP_444253.3
	MYLK	NM_053027.4		c.5562T>G	p.Gly1854Gly	synonymous	Exon 33 of 33	NP_444255.3
	MYLK	NM_053026.4		c.5508T>G	p.Gly1836Gly	synonymous	Exon 33 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.5715T>G	p.Gly1905Gly	synonymous	Exon 34 of 34	ENSP00000353452.3	Q15746-1
	MYLK	ENST00000418370.6	TSL:1	c.435T>G	p.Gly145Gly	synonymous	Exon 3 of 3	ENSP00000428967.1	Q15746-8
	MYLK	ENST00000578202.2	TSL:1	c.*220T>G		3_prime_UTR	Exon 3 of 3	ENSP00000463691.2	A0A8J9G5A3

Frequencies

GnomAD3 genomes AF: 0.0000609 AC: 9 AN: 147742 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251320 AF XY: 0.0000221

Gnomad AFR exome AF: 0.0000615

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000111 AC: 162 AN: 1461840 Hom.: 0 Cov.: 36 AF XY: 0.000106 AC XY: 77 AN XY: 727240

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000232 AC: 2 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000132 AC: 147 AN: 1111994

Other (OTH) AF: 0.000215 AC: 13 AN: 60384

GnomAD4 genome AF: 0.0000609 AC: 9 AN: 147742 Hom.: 0 Cov.: 31 AF XY: 0.0000139 AC XY: 1 AN XY: 71710

African (AFR) AF: 0.0000504 AC: 2 AN: 39720

American (AMR) AF: 0.00 AC: 0 AN: 14602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3442

East Asian (EAS) AF: 0.00 AC: 0 AN: 5054

South Asian (SAS) AF: 0.00 AC: 0 AN: 4682

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9774

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 304

European-Non Finnish (NFE) AF: 0.000104 AC: 7 AN: 67212

Other (OTH) AF: 0.00 AC: 0 AN: 2054

Alfa AF: 0.0000975 Hom.: 0

EpiCase AF: 0.000218

EpiControl AF: 0.0000593

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.47
DANN	Benign	0.51
PhyloP100		-0.84
Mutation Taster		=100/0	polymorphism

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: rs753024354; hg19: chr3-123332982; COSMIC: COSV60606621; COSMIC: COSV60606621;