chr3-123703970-G-C

Position:

• chr3-123703970-G-C

Variant summary

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

The NM_053025.4(MYLK):​c.2391-2461C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 152,230 control chromosomes in the GnomAD database, including 2,713 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 0.12 (2713 hom., cov: 33)
• Consequence: MYLK NM_053025.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.42

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]

ENSG00000288806 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYLK	NM_053025.4	c.2391-2461C>G		intron_variant		ENST00000360304.8	NP_444253.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8	c.2391-2461C>G		intron_variant		5	NM_053025.4	ENSP00000353452.3

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18642 AN: 152112 Hom.: 2696 Cov.: 33

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0618

Gnomad ASJ AF: 0.0271

Gnomad EAS AF: 0.539

Gnomad SAS AF: 0.267

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0161

Gnomad OTH AF: 0.102

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18705 AN: 152230 Hom.: 2713 Cov.: 33 AF XY: 0.128 AC XY: 9558 AN XY: 74434

Gnomad4 AFR AF: 0.274

Gnomad4 AMR AF: 0.0616

Gnomad4 ASJ AF: 0.0271

Gnomad4 EAS AF: 0.538

Gnomad4 SAS AF: 0.267

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.0161

Gnomad4 OTH AF: 0.110

Alfa AF: 0.00847 Hom.: 8

Bravo AF: 0.128

Asia WGS AF: 0.413 AC: 1433 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.19
DANN	Benign	0.35

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: rs936170; hg19: chr3-123422817;