rs820463

Variant names:

• chr3-123638190-A-G
• rs820463
• NM_053025.4:c.4842T>C

Your query was ambiguous. Multiple possible variants found:

• chr3-123638190-A-G
• chr3-123638190-A-T

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.4842T>C​(p.Asn1614Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,612,880 control chromosomes in the GnomAD database, including 30,210 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (6022 hom., cov: 32)
  • Exomes 𝑓: 0.13 (24188 hom.)
• Consequence: MYLK NM_053025.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:12
• Conservation: PhyloP100: 0.0920
• Publications: 21 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 3-123638190-A-G is Benign according to our data. Variant chr3-123638190-A-G is described in ClinVar as Benign. ClinVar VariationId is 226771.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.092 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.603 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.4842T>C	p.Asn1614Asn	synonymous	Exon 29 of 34	NP_444253.3
	MYLK	NM_053027.4		c.4842T>C	p.Asn1614Asn	synonymous	Exon 29 of 33	NP_444255.3
	MYLK	NM_053026.4		c.4635T>C	p.Asn1545Asn	synonymous	Exon 28 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.4842T>C	p.Asn1614Asn	synonymous	Exon 29 of 34	ENSP00000353452.3
	MYLK	ENST00000464489.5	TSL:1	n.*4421T>C		non_coding_transcript_exon	Exon 28 of 33	ENSP00000417798.1
	MYLK	ENST00000464489.5	TSL:1	n.*4421T>C		3_prime_UTR	Exon 28 of 33	ENSP00000417798.1

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34032 AN: 151920 Hom.: 5995 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.0340

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.620

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.0691

Gnomad MID AF: 0.182

Gnomad NFE AF: 0.0852

Gnomad OTH AF: 0.198

GnomAD2 exomes AF: 0.220 AC: 55157 AN: 250898 AF XY: 0.208

Gnomad AFR exome AF: 0.425

Gnomad AMR exome AF: 0.417

Gnomad ASJ exome AF: 0.134

Gnomad EAS exome AF: 0.608

Gnomad FIN exome AF: 0.0804

Gnomad NFE exome AF: 0.0873

Gnomad OTH exome AF: 0.178

GnomAD4 exome AF: 0.130 AC: 189516 AN: 1460842 Hom.: 24188 Cov.: 33 AF XY: 0.132 AC XY: 96137 AN XY: 726720

African (AFR) AF: 0.432 AC: 14434 AN: 33430

American (AMR) AF: 0.404 AC: 18011 AN: 44636

Ashkenazi Jewish (ASJ) AF: 0.137 AC: 3584 AN: 26120

East Asian (EAS) AF: 0.644 AC: 25568 AN: 39678

South Asian (SAS) AF: 0.282 AC: 24292 AN: 86190

European-Finnish (FIN) AF: 0.0787 AC: 4202 AN: 53412

Middle Eastern (MID) AF: 0.184 AC: 1002 AN: 5442

European-Non Finnish (NFE) AF: 0.0798 AC: 88759 AN: 1111608

Other (OTH) AF: 0.160 AC: 9664 AN: 60326

GnomAD4 genome AF: 0.224 AC: 34128 AN: 152038 Hom.: 6022 Cov.: 32 AF XY: 0.228 AC XY: 16931 AN XY: 74316

African (AFR) AF: 0.419 AC: 17324 AN: 41390

American (AMR) AF: 0.299 AC: 4571 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 487 AN: 3470

East Asian (EAS) AF: 0.621 AC: 3179 AN: 5120

South Asian (SAS) AF: 0.317 AC: 1528 AN: 4826

European-Finnish (FIN) AF: 0.0691 AC: 734 AN: 10620

Middle Eastern (MID) AF: 0.188 AC: 55 AN: 292

European-Non Finnish (NFE) AF: 0.0852 AC: 5791 AN: 68008

Other (OTH) AF: 0.202 AC: 428 AN: 2114

Alfa AF: 0.147 Hom.: 4469

Bravo AF: 0.252

Asia WGS AF: 0.459 AC: 1593 AN: 3478

EpiCase AF: 0.0895

EpiControl AF: 0.0911

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.053
DANN	Benign	0.55
PhyloP100		0.092
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: rs820463; hg19: chr3-123357037; COSMIC: COSV60607062; COSMIC: COSV60607062;