chr3-123700066-G-A

Variant names:

• chr3-123700066-G-A
• rs865358
• NM_053025.4:c.3402C>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.3402C>T​(p.Asn1134Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.989 in 1,613,902 control chromosomes in the GnomAD database, including 789,789 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.95 (68730 hom., cov: 29)
  • Exomes 𝑓: 0.99 (721059 hom.)
• Consequence: MYLK NM_053025.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: 2.47
• Publications: 18 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=-0.49).
• BP6: Variant 3-123700066-G-A is Benign according to our data. Variant chr3-123700066-G-A is described in ClinVar as Benign. ClinVar VariationId is 194903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=2.47 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.991 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.3402C>T	p.Asn1134Asn	synonymous	Exon 18 of 34	NP_444253.3
	MYLK	NM_053027.4		c.3402C>T	p.Asn1134Asn	synonymous	Exon 18 of 33	NP_444255.3
	MYLK	NM_053026.4		c.3195C>T	p.Asn1065Asn	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.3402C>T	p.Asn1134Asn	synonymous	Exon 18 of 34	ENSP00000353452.3	Q15746-1
	MYLK	ENST00000504946.6	TSL:1	c.1011C>T	p.Asn337Asn	synonymous	Exon 2 of 4	ENSP00000510315.1	A0A8I5KYZ0
	MYLK	ENST00000464489.5	TSL:1	n.*2981C>T		non_coding_transcript_exon	Exon 17 of 33	ENSP00000417798.1	F8WBL7

Frequencies

GnomAD3 genomes AF: 0.948 AC: 143999 AN: 151896 Hom.: 68696 Cov.: 29

Gnomad AFR AF: 0.826

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.974

Gnomad ASJ AF: 0.988

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.998

Gnomad FIN AF: 1.00

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.953

GnomAD2 exomes AF: 0.985 AC: 247623 AN: 251454 AF XY: 0.988

Gnomad AFR exome AF: 0.827

Gnomad AMR exome AF: 0.987

Gnomad ASJ exome AF: 0.985

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 1.00

Gnomad NFE exome AF: 0.998

Gnomad OTH exome AF: 0.987

GnomAD4 exome AF: 0.993 AC: 1451405 AN: 1461888 Hom.: 721059 Cov.: 70 AF XY: 0.993 AC XY: 722475 AN XY: 727246

African (AFR) AF: 0.827 AC: 27684 AN: 33478

American (AMR) AF: 0.984 AC: 44002 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.984 AC: 25715 AN: 26136

East Asian (EAS) AF: 1.00 AC: 39698 AN: 39700

South Asian (SAS) AF: 0.998 AC: 86083 AN: 86258

European-Finnish (FIN) AF: 1.00 AC: 53420 AN: 53420

Middle Eastern (MID) AF: 0.978 AC: 5640 AN: 5768

European-Non Finnish (NFE) AF: 0.998 AC: 1109737 AN: 1112008

Other (OTH) AF: 0.984 AC: 59426 AN: 60396

GnomAD4 genome AF: 0.948 AC: 144087 AN: 152014 Hom.: 68730 Cov.: 29 AF XY: 0.950 AC XY: 70597 AN XY: 74340

African (AFR) AF: 0.826 AC: 34189 AN: 41390

American (AMR) AF: 0.974 AC: 14887 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.988 AC: 3427 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5138 AN: 5138

South Asian (SAS) AF: 0.998 AC: 4781 AN: 4792

European-Finnish (FIN) AF: 1.00 AC: 10608 AN: 10608

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67850 AN: 68012

Other (OTH) AF: 0.953 AC: 2011 AN: 2110

Alfa AF: 0.971 Hom.: 47969

Bravo AF: 0.940

Asia WGS AF: 0.989 AC: 3439 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	4	Aortic aneurysm, familial thoracic 7 (4)
-	-	2	not provided (2)
-	-	1	Familial thoracic aortic aneurysm and aortic dissection (1)
-	-	1	Megacystis, microcolon, hypoperistalsis syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	6.2
DANN	Benign	0.67
PhyloP100		2.5
Mutation Taster		=98/2	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: rs865358; hg19: chr3-123418913; COSMIC: COSV108183000; COSMIC: COSV108183000;