rs2700352

chr3-123831616-G-Achr3-123831616-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_053025.4(MYLK):c.-72C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.177 in 290,724 control chromosomes in the GnomAD database, including 5,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2249 hom., cov: 32)
  • Exomes 𝑓: 0.19 (2855 hom.)
• Consequence: MYLK NM_053025.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.34

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-123831616-G-A is Benign according to our data. Variant chr3-123831616-G-A is described in ClinVar as [Benign]. Clinvar id is 342911.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.214 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK	NM_053025.4	c.-72C>T		5_prime_UTR_variant	3/34	ENST00000360304.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK	ENST00000360304.8	c.-72C>T		5_prime_UTR_variant	3/34	5	NM_053025.4	P4

Frequencies

GnomAD3 genomes AF: 0.165 AC: 25096 AN: 152020 Hom.: 2246 Cov.: 32

Gnomad AFR AF: 0.114

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.0452

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.217

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.167

GnomAD4 exome AF: 0.190 AC: 26287 AN: 138586 Hom.: 2855 Cov.: 3 AF XY: 0.195 AC XY: 14523 AN XY: 74586

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.124

Gnomad4 ASJ exome AF: 0.187

Gnomad4 EAS exome AF: 0.0419

Gnomad4 SAS exome AF: 0.241

Gnomad4 FIN exome AF: 0.214

Gnomad4 NFE exome AF: 0.190

Gnomad4 OTH exome AF: 0.199

GnomAD4 genome AF: 0.165 AC: 25118 AN: 152138 Hom.: 2249 Cov.: 32 AF XY: 0.165 AC XY: 12298 AN XY: 74356

Gnomad4 AFR AF: 0.114

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.195

Gnomad4 EAS AF: 0.0453

Gnomad4 SAS AF: 0.225

Gnomad4 FIN AF: 0.217

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.172

Alfa AF: 0.186 Hom.: 2806

Bravo AF: 0.153

Asia WGS AF: 0.156 AC: 543 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Aortic aneurysm, familial thoracic 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Nov 29, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	14
Dann	Benign	0.83

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: rs2700352; hg19: chr3-123550463;