16-46707704-T-G

Variant names:

• chr16-46707704-T-G
• NM_182493.3:c.2460A>C

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PM4

The NM_182493.3(MYLK3):​c.2460A>C​(p.Ter820Tyrext*?) variant causes a stop lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYLK3 NM_182493.3 stop_lost
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.76
• 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Stoplost variant in NM_182493.3 Downstream stopcodon found after 29 codons.

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.2460A>C	p.Ter820Tyrext*?	stop_lost	Exon 13 of 13	NP_872299.2	Q32MK0-3
	MYLK3	NM_001308301.1		c.1437A>C	p.Ter479Tyrext*?	stop_lost	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.2460A>C	p.Ter820Tyrext*?	stop_lost	Exon 13 of 13	ENSP00000378288.4	Q32MK0-3
	MYLK3	ENST00000874186.1		c.2463A>C	p.Ter821Tyrext*?	stop_lost	Exon 13 of 13	ENSP00000544245.1
	MYLK3	ENST00000874187.1		c.2460A>C	p.Ter820Tyrext*?	stop_lost	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
PhyloP100		4.8

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-46741616;