3-123622031-A-G

Variant names:

• chr3-123622031-A-G
• rs820455
• ENST00000418370.6:c.-1737T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000418370.6(MYLK):​c.-1737T>C variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 152,174 control chromosomes in the GnomAD database, including 347 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.057 (347 hom., cov: 33)
  • Exomes 𝑓: 0.019 (0 hom.)
• Consequence: MYLK ENST00000418370.6 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.56

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.225 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK	NM_053025.4	c.5239-1695T>C		intron_variant	Intron 31 of 33	ENST00000360304.8	NP_444253.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8	c.5239-1695T>C		intron_variant	Intron 31 of 33	5	NM_053025.4	ENSP00000353452.3

Frequencies

GnomAD3 genomes AF: 0.0568 AC: 8631 AN: 152004 Hom.: 345 Cov.: 33

Gnomad AFR AF: 0.0493

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0560

Gnomad ASJ AF: 0.0410

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0273

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0496

Gnomad OTH AF: 0.0512

GnomAD4 exome AF: 0.0192 AC: 1 AN: 52 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 36

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0294

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0568 AC: 8642 AN: 152122 Hom.: 347 Cov.: 33 AF XY: 0.0578 AC XY: 4299 AN XY: 74374

Gnomad4 AFR AF: 0.0492

Gnomad4 AMR AF: 0.0559

Gnomad4 ASJ AF: 0.0410

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0273

Gnomad4 NFE AF: 0.0497

Gnomad4 OTH AF: 0.0540

Alfa AF: 0.0495 Hom.: 34

Bravo AF: 0.0596

Asia WGS AF: 0.171 AC: 593 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.50
DANN	Benign	0.62

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: rs820455; hg19: chr3-123340878;