Variant 3-123700066-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_053025.4(MYLK):c.3402C>A(p.Asn1134Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N1134N) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 29)

Failed GnomAD Quality Control

Consequence

MYLK
NM_053025.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.47

Variant links:

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 links:

LOC105369194 (HGNC:):

LOC105369194 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant where missense usually causes diseases, MYLK

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYLK	NM_053025.4 linkuse as main transcript	c.3402C>A	p.Asn1134Lys	missense_variant	18/34	ENST00000360304.8
LOC105369194	XR_924417.4 linkuse as main transcript	n.108-3800G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYLK	ENST00000360304.8 linkuse as main transcript	c.3402C>A	p.Asn1134Lys	missense_variant	18/34	5	NM_053025.4	P4	Q15746-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151924

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

151924

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74220

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.76

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.11

Eigen_PC

Benign

0.091

FATHMM_MKL

Uncertain

0.89

M_CAP

Benign

0.025

MetaRNN

Uncertain

0.68

D;D;D;D;D;D

MetaSVM

Benign

-0.63

MutationAssessor

Benign

2.0

M;.;M;M;.;M

MutationTaster

Benign

0.084

P;P;P;P;P

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-2.3

N;.;N;N;N;N

REVEL

Uncertain

0.32

Sift

Uncertain

0.0070

D;.;D;D;D;D

Sift4G

Uncertain

0.0030

D;D;D;D;D;D

Polyphen

0.96

D;D;D;P;D;P

Vest4

0.37

MutPred

0.72

Gain of methylation at N1134 (P = 0.0126);.;Gain of methylation at N1134 (P = 0.0126);Gain of methylation at N1134 (P = 0.0126);.;Gain of methylation at N1134 (P = 0.0126);

MVP

0.69

MPC

0.19

ClinPred

0.75

GERP RS

2.1

Varity_R

0.15

gMVP

0.47

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over