3-123612928-TA-T

Variant names:

• chr3-123612928-TA-T
• rs34709307
• NM_053025.4:c.*1176delT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_053025.4(MYLK):​c.*1176delT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.171 in 147,852 control chromosomes in the GnomAD database, including 4,928 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (4928 hom., cov: 31)
  • Exomes 𝑓: 0.014 (0 hom.)
• Consequence: MYLK NM_053025.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.18
• Publications: 5 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 -10 ACMG points.

• BP6: Variant 3-123612928-TA-T is Benign according to our data. Variant chr3-123612928-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 342836.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK	NM_053025.4	c.*1176delT		3_prime_UTR_variant	Exon 34 of 34	ENST00000360304.8	NP_444253.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8	c.*1176delT		3_prime_UTR_variant	Exon 34 of 34	5	NM_053025.4	ENSP00000353452.3

Frequencies

GnomAD3 genomes AF: 0.171 AC: 25183 AN: 147306 Hom.: 4914 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.242

Gnomad ASJ AF: 0.0395

Gnomad EAS AF: 0.465

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.0153

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.00518

Gnomad OTH AF: 0.145

GnomAD4 exome AF: 0.0138 AC: 6 AN: 434 Hom.: 0 Cov.: 0 AF XY: 0.0154 AC XY: 4 AN XY: 260

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0140 AC: 6 AN: 428

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AF: 0.00 AC: 0 AN: 4

GnomAD4 genome AF: 0.171 AC: 25241 AN: 147418 Hom.: 4928 Cov.: 31 AF XY: 0.173 AC XY: 12386 AN XY: 71776

African (AFR) AF: 0.446 AC: 18310 AN: 41044

American (AMR) AF: 0.243 AC: 3554 AN: 14614

Ashkenazi Jewish (ASJ) AF: 0.0395 AC: 135 AN: 3414

East Asian (EAS) AF: 0.465 AC: 1820 AN: 3914

South Asian (SAS) AF: 0.146 AC: 603 AN: 4130

European-Finnish (FIN) AF: 0.0153 AC: 160 AN: 10440

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.00518 AC: 345 AN: 66644

Other (OTH) AF: 0.147 AC: 296 AN: 2012

Alfa AF: 0.0919 Hom.: 318

Bravo AF: 0.195

Asia WGS AF: 0.222 AC: 727 AN: 3268

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2
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: rs34709307; hg19: chr3-123331775;