rs820336

chr3-123696934-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_053025.4(MYLK):c.3448+3086G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.542 in 152,174 control chromosomes in the GnomAD database, including 27,836 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.54 (27836 hom., cov: 33)
• Consequence: MYLK NM_053025.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.12

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]

LOC105369194 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 3-123696934-C-T is Benign according to our data. Variant chr3-123696934-C-T is described in ClinVar as [Benign]. Clinvar id is 1168972.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK	NM_053025.4	c.3448+3086G>A		intron_variant		ENST00000360304.8
LOC105369194	XR_924417.4	n.107+4012C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK	ENST00000360304.8	c.3448+3086G>A		intron_variant		5	NM_053025.4	P4

Frequencies

GnomAD3 genomes AF: 0.543 AC: 82558 AN: 152056 Hom.: 27838 Cov.: 33

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.535

Gnomad ASJ AF: 0.765

Gnomad EAS AF: 0.0465

Gnomad SAS AF: 0.463

Gnomad FIN AF: 0.638

Gnomad MID AF: 0.706

Gnomad NFE AF: 0.773

Gnomad OTH AF: 0.583

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

GnomAD4 genome AF: 0.542 AC: 82552 AN: 152174 Hom.: 27836 Cov.: 33 AF XY: 0.533 AC XY: 39628 AN XY: 74382

Gnomad4 AFR AF: 0.187

Gnomad4 AMR AF: 0.534

Gnomad4 ASJ AF: 0.765

Gnomad4 EAS AF: 0.0463

Gnomad4 SAS AF: 0.463

Gnomad4 FIN AF: 0.638

Gnomad4 NFE AF: 0.773

Gnomad4 OTH AF: 0.579

Alfa AF: 0.729 Hom.: 54272

Bravo AF: 0.519

Asia WGS AF: 0.267 AC: 934 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Aortic aneurysm, familial thoracic 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 19, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.10
Dann	Benign	0.81

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: rs820336; hg19: chr3-123415781;