Genetic Variant MYL1:c.304+77_304+80dupGTGT (chr2-210298339-T-TACAC) – 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+77_304+80dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 1,176,114 control chromosomes in the GnomAD database, including 53 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0099 ( 22 hom., cov: 0)

Exomes 𝑓: 0.022 ( 31 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 GnomAd4 at 22 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+77_304+80dupGTGT		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.172+77_172+80dupGTGT		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+81insGTGT	intron	N/A	ENSP00000307280.4	P05976-1
MYL1	ENST00000341685.8	TSL:1	c.172+80_172+81insGTGT	intron	N/A	ENSP00000343321.4	P05976-2
MYL1	ENST00000957378.1		c.268+80_268+81insGTGT	intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes

AF:

0.00991

AC:

1460

AN:

147260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00893

Gnomad AMI

AF:

0.0940

Gnomad AMR

AF:

0.00592

Gnomad ASJ

AF:

0.0123

Gnomad EAS

AF:

0.00490

Gnomad SAS

AF:

0.00575

Gnomad FIN

AF:

0.0347

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00720

Gnomad OTH

AF:

0.00939

GnomAD4 exome

AF:

0.0220

AC:

22640

AN:

1028748

Hom.:

AF XY:

0.0223

AC XY:

11686

AN XY:

524100

show subpopulations

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

African (AFR)

AF:

0.0149

AC:

390

AN:

26150

American (AMR)

AF:

0.0263

AC:

1091

AN:

41438

Ashkenazi Jewish (ASJ)

AF:

0.0351

AC:

729

AN:

20796

East Asian (EAS)

AF:

0.0146

AC:

516

AN:

35372

South Asian (SAS)

AF:

0.0261

AC:

1843

AN:

70530

European-Finnish (FIN)

AF:

0.0437

AC:

1929

AN:

44162

Middle Eastern (MID)

AF:

0.0415

AC:

160

AN:

3852

European-Non Finnish (NFE)

AF:

0.0201

AC:

14880

AN:

741182

Other (OTH)

AF:

0.0243

AC:

1102

AN:

45266

⚠️ 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: 0.336

Heterozygous variant carriers

1402

2804

4205

5607

7009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.00993

AC:

1464

AN:

147366

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

798

AN XY:

71594

show subpopulations

African (AFR)

AF:

0.00893

AC:

356

AN:

39854

American (AMR)

AF:

0.00598

AC:

AN:

14722

Ashkenazi Jewish (ASJ)

AF:

0.0123

AC:

AN:

3428

East Asian (EAS)

AF:

0.00492

AC:

AN:

4882

South Asian (SAS)

AF:

0.00598

AC:

AN:

4516

European-Finnish (FIN)

AF:

0.0347

AC:

341

AN:

9836

Middle Eastern (MID)

AF:

0.00

AC:

AN:

286

European-Non Finnish (NFE)

AF:

0.00720

AC:

482

AN:

66900

Other (OTH)

AF:

0.00977

AC:

AN:

2048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

136

203

271

339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00968

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-TACACACACACACACACAC

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