3-123700312-ATTGCCCATGGGCTTCAGGGTCTCGGCAGGCTTGGCG-ATTGCCCATGGGCTTCAGGGTCTCGGCAGGCTTGGCGTTGCCCATGGGCTTCAGGGTCTCGGCAGGCTTGGCG

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM4

The NM_053025.4(MYLK):c.3120_3155dupCGCCAAGCCTGCCGAGACCCTGAAGCCCATGGGCAA(p.Asn1052_Ala1053insAlaLysProAlaGluThrLeuLysProMetGlyAsn) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. N1052N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 30)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MYLK
NM_053025.4 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.50

Publications

0 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: Uncertain_significance. The variant received 2 ACMG points.

PM4

Nonframeshift variant in NON repetitive region in NM_053025.4.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053025.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYLK	NM_053025.4	MANE Select	c.3120_3155dupCGCCAAGCCTGCCGAGACCCTGAAGCCCATGGGCAA	p.Asn1052_Ala1053insAlaLysProAlaGluThrLeuLysProMetGlyAsn	disruptive_inframe_insertion	Exon 18 of 34	NP_444253.3
MYLK	NM_053027.4		c.3120_3155dupCGCCAAGCCTGCCGAGACCCTGAAGCCCATGGGCAA	p.Asn1052_Ala1053insAlaLysProAlaGluThrLeuLysProMetGlyAsn	disruptive_inframe_insertion	Exon 18 of 33	NP_444255.3
MYLK	NM_053026.4		c.2913_2948dupCGCCAAGCCTGCCGAGACCCTGAAGCCCATGGGCAA	p.Asn983_Ala984insAlaLysProAlaGluThrLeuLysProMetGlyAsn	disruptive_inframe_insertion	Exon 17 of 33	NP_444254.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYLK	ENST00000360304.8	TSL:5 MANE Select	c.3120_3155dupCGCCAAGCCTGCCGAGACCCTGAAGCCCATGGGCAA	p.Asn1052_Ala1053insAlaLysProAlaGluThrLeuLysProMetGlyAsn	disruptive_inframe_insertion	Exon 18 of 34	ENSP00000353452.3	Q15746-1
MYLK	ENST00000504946.6	TSL:1	c.729_764dupCGCCAAGCCTGCCGAGACCCTGAAGCCCATGGGCAA	p.Asn255_Ala256insAlaLysProAlaGluThrLeuLysProMetGlyAsn	disruptive_inframe_insertion	Exon 2 of 4	ENSP00000510315.1	A0A8I5KYZ0
MYLK	ENST00000464489.5	TSL:1	n.2699_2734dupCGCCAAGCCTGCCGAGACCCTGAAGCCCATGGGCAA		non_coding_transcript_exon	Exon 17 of 33	ENSP00000417798.1	F8WBL7

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

6.84e-7

AC:

AN:

1461754

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727162

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86230

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1111924

Other (OTH)

AF:

0.00

AC:

AN:

60386

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.375

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Aortic aneurysm, familial thoracic 7 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.5

Splicing

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over