NM_182493.3:c.2414T>G

Variant names:

• chr16-46707750-A-C
• NM_182493.3:c.2414T>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182493.3(MYLK3):​c.2414T>G​(p.Val805Gly) 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. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V805A) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYLK3 NM_182493.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.79
• Publications: 0 publications found

Genes affected

MYLK3 (HGNC:29826): (myosin light chain kinase 3) Phosphorylation of cardiac myosin heavy chains (see MYH7B, MIM 609928) and light chains (see MYL2, MIM 160781) by a kinase, such as MYLK3, potentiates the force and rate of cross-bridge recruitment in cardiac myocytes (Chan et al., 2008 [PubMed 18202317]).[supplied by OMIM, Jul 2008]

MYLK3 Gene-Disease associations (from GenCC):

• dilated cardiomyopathy

  Inheritance: AD, AR Classification: MODERATE Submitted by: ClinGen, Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.239835).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182493.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK3	NM_182493.3	MANE Select	c.2414T>G	p.Val805Gly	missense	Exon 13 of 13	NP_872299.2	Q32MK0-3
	MYLK3	NM_001308301.1		c.1391T>G	p.Val464Gly	missense	Exon 12 of 12	NP_001295230.1	Q32MK0-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYLK3	ENST00000394809.9	TSL:1 MANE Select	c.2414T>G	p.Val805Gly	missense	Exon 13 of 13	ENSP00000378288.4	Q32MK0-3
	MYLK3	ENST00000874186.1		c.2417T>G	p.Val806Gly	missense	Exon 13 of 13	ENSP00000544245.1
	MYLK3	ENST00000874187.1		c.2414T>G	p.Val805Gly	missense	Exon 13 of 13	ENSP00000544246.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.33	T
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.00058
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.49	T
M_CAP	Benign	0.063	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.74	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.8
PrimateAI	Benign	0.34	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.38
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.35	T
Polyphen		0.25	B
Vest4		0.56
MutPred		0.49		Loss of stability (P = 0.0076)
MVP		0.61
MPC		0.68
ClinPred		0.72	D
GERP RS		2.9
Varity_R		0.30
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr16-46741662;