3-123612928-TA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_053025.4(MYLK):c.*1176del 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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MYLK	NM_053025.4	c.*1176del		3_prime_UTR_variant	34/34	ENST00000360304.8
MYLK-AS1	NR_038266.2	n.290-16564del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK	ENST00000360304.8	c.*1176del		3_prime_UTR_variant	34/34	5	NM_053025.4	P4
MYLK-AS1	ENST00000485162.5	n.261-16564del		intron_variant, non_coding_transcript_variant		4

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

Gnomad4 FIN exome AF: 0.0140

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

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

Gnomad4 AFR AF: 0.446

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.0395

Gnomad4 EAS AF: 0.465

Gnomad4 SAS AF: 0.146

Gnomad4 FIN AF: 0.0153

Gnomad4 NFE AF: 0.00518

Gnomad4 OTH AF: 0.147

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

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs34709307; hg19: chr3-123331775;