3-123612839-TACAC-T

Position:

• chr3-123612839-TACAC-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_053025.4(MYLK):​c.*1262_*1265del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00204 in 152,046 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYLK NM_053025.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.38

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK	NM_053025.4	c.*1262_*1265del		3_prime_UTR_variant	34/34	ENST00000360304.8	NP_444253.3
MYLK-AS1	NR_038266.2	n.290-16645_290-16642del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8	c.*1262_*1265del		3_prime_UTR_variant	34/34	5	NM_053025.4	ENSP00000353452	P4
MYLK-AS1	ENST00000485162.5	n.261-16645_261-16642del		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.00203 AC: 309 AN: 151930 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00387

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00404

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00274

Gnomad OTH AF: 0.00144

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 434 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 262

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00204 AC: 310 AN: 152046 Hom.: 0 Cov.: 33 AF XY: 0.00213 AC XY: 158 AN XY: 74348

Gnomad4 AFR AF: 0.000265

Gnomad4 AMR AF: 0.00386

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.00405

Gnomad4 SAS AF: 0.000829

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00274

Gnomad4 OTH AF: 0.00142

Bravo AF: 0.00221

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Familial thoracic aortic aneurysm and aortic dissection Uncertain:1

Uncertain significance, 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: rs550448371; hg19: chr3-123331686;