Genetic Variant MYL1:c.304+67_304+80dupGTGTGTGTGTGTGT (chr2-210298339-T-TACACACACACACAC) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_079420.3(MYL1):c.304+67_304+80dupGTGTGTGTGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000344 in 1,187,766 control chromosomes in the GnomAD database, including 3 homozygotes. 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00028 ( 1 hom., cov: 0)

Exomes 𝑓: 0.00035 ( 2 hom. )

Consequence

MYL1
NM_079420.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.73

Publications

0 publications found

Variant links:

Genes affected

MYL1 (HGNC:7582): (myosin light chain 1) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in fast skeletal muscle. Two transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

MYL1 Gene-Disease associations (from GenCC):

congenital myopathy with reduced type 2 muscle fibers
Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
congenital myopathy
Inheritance: AR Classification: LIMITED Submitted by: ClinGen

MYL1 links:

ENSG00000279317 (HGNC:):

ENSG00000279317 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 2 Unknown,AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_079420.3. 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
	MYL1	NM_079420.3	MANE Select	c.304+67_304+80dupGTGTGTGTGTGTGT		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.172+67_172+80dupGTGTGTGTGTGTGT		intron	N/A	NP_524146.1	P05976-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYL1	ENST00000352451.4	TSL:1 MANE Select	c.304+80_304+81insGTGTGTGTGTGTGT	intron	N/A	ENSP00000307280.4	P05976-1
MYL1	ENST00000341685.8	TSL:1	c.172+80_172+81insGTGTGTGTGTGTGT	intron	N/A	ENSP00000343321.4	P05976-2
MYL1	ENST00000957378.1		c.268+80_268+81insGTGTGTGTGTGTGT	intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes

AF:

0.000278

AC:

AN:

147310

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000272

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00354

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000314

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000352

AC:

366

AN:

1040348

Hom.:

AF XY:

0.000413

AC XY:

219

AN XY:

530312

show subpopulations

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

African (AFR)

AF:

0.000190

AC:

AN:

26302

American (AMR)

AF:

0.000640

AC:

AN:

42216

Ashkenazi Jewish (ASJ)

AF:

0.0000471

AC:

AN:

21212

East Asian (EAS)

AF:

0.0000839

AC:

AN:

35754

South Asian (SAS)

AF:

0.00248

AC:

178

AN:

71646

European-Finnish (FIN)

AF:

0.000157

AC:

AN:

44690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3954

European-Non Finnish (NFE)

AF:

0.000162

AC:

121

AN:

748692

Other (OTH)

AF:

0.000523

AC:

AN:

45882

⚠️ 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: 0.382

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000285

AC:

AN:

147418

Hom.:

Cov.:

AF XY:

0.000335

AC XY:

AN XY:

71628

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

39860

American (AMR)

AF:

0.000272

AC:

AN:

14728

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00

AC:

AN:

4882

South Asian (SAS)

AF:

0.00376

AC:

AN:

4518

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9854

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000314

AC:

AN:

66914

Other (OTH)

AF:

0.00

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

299

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

-1.7

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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2-210298339-TACACACACACACAC-TACACACACACACACACACACACACACAC

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over