3-123696934-C-T

Variant names:

• chr3-123696934-C-T
• rs820336
• NM_053025.4:c.3448+3086G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 16 publications found

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)

LOC105369194 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
MYLK	NM_053025.4	c.3448+3086G>A		intron_variant	Intron 18 of 33	ENST00000360304.8	NP_444253.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8	c.3448+3086G>A		intron_variant	Intron 18 of 33	5	NM_053025.4	ENSP00000353452.3

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

African (AFR) AF: 0.187 AC: 7747 AN: 41524

American (AMR) AF: 0.534 AC: 8171 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.765 AC: 2654 AN: 3470

East Asian (EAS) AF: 0.0463 AC: 239 AN: 5166

South Asian (SAS) AF: 0.463 AC: 2231 AN: 4818

European-Finnish (FIN) AF: 0.638 AC: 6749 AN: 10584

Middle Eastern (MID) AF: 0.707 AC: 208 AN: 294

European-Non Finnish (NFE) AF: 0.773 AC: 52585 AN: 68002

Other (OTH) AF: 0.579 AC: 1221 AN: 2108

Alfa AF: 0.689 Hom.: 116259

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

Jan 27, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.10
DANN	Benign	0.81
PhyloP100		-3.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs820336; hg19: chr3-123415781;