dbSNP rs75370906: MYLK:p.Thr1085Ser (chr3-123700215-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_053025.4(MYLK):c.3253A>T(p.Thr1085Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1085A) has been classified as Benign.

Frequency

Genomes: not found (cov: 30)

Consequence

MYLK
NM_053025.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.373

Publications

7 publications found

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:

MYLK-AS1 (HGNC:42440): (MYLK antisense RNA 1)

MYLK-AS1 links:

LOC105369194 (HGNC:):

LOC105369194 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06555316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYLK	NM_053025.4 link	c.3253A>T	p.Thr1085Ser	missense_variant	Exon 18 of 34	ENST00000360304.8	NP_444253.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYLK	ENST00000360304.8 link	c.3253A>T	p.Thr1085Ser	missense_variant	Exon 18 of 34	5	NM_053025.4	ENSP00000353452.3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

124

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.46

CADD

Benign

9.1

(source)

DANN

Benign

0.70

DEOGEN2

Benign

0.19

.;.;.;T;.;T

Eigen

Benign

-0.90

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.78

.;T;T;T;.;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.066

T;T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

1.9

L;.;L;L;.;L

PhyloP100

-0.37

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.53

N;.;N;N;N;N

REVEL

Benign

0.034

Sift

Benign

0.29

T;.;T;T;T;T

Sift4G

Uncertain

0.047

D;D;D;D;D;D

Polyphen

0.0050

B;B;B;B;B;B

Vest4

0.070

MutPred

0.12

Loss of glycosylation at T1085 (P = 0.0618);.;Loss of glycosylation at T1085 (P = 0.0618);Loss of glycosylation at T1085 (P = 0.0618);.;Loss of glycosylation at T1085 (P = 0.0618);

MVP

0.59

MPC

0.15

ClinPred

0.075

GERP RS

0.61

Varity_R

0.063

gMVP

0.066

Mutation Taster

=90/10

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over