Genetic Variant MYL1:c.-78T>A (chr2-210303622-A-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The ENST00000341685.8(MYL1):c.-78T>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000885 in 1,581,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000049 ( 0 hom. )

Consequence

MYL1
ENST00000341685.8 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.69

Publications

10 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 -2 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.46).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000341685.8. 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.133-1107T>A		intron	N/A	NP_524144.1	P05976-1
	MYL1	NM_079422.3		c.-78T>A		upstream_gene	N/A	NP_524146.1	P05976-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYL1	ENST00000341685.8	TSL:1	c.-78T>A	5_prime_UTR	Exon 1 of 7	ENSP00000343321.4	P05976-2
MYL1	ENST00000352451.4	TSL:1 MANE Select	c.133-1107T>A	intron	N/A	ENSP00000307280.4	P05976-1
MYL1	ENST00000957378.1		c.133-1107T>A	intron	N/A	ENSP00000627437.1

Frequencies

GnomAD3 genomes

AF:

0.0000461

AC:

AN:

151928

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.00000490

AC:

AN:

1429118

Hom.:

Cov.:

AF XY:

0.00000141

AC XY:

AN XY:

710344

show subpopulations

African (AFR)

AF:

0.000223

AC:

AN:

31438

American (AMR)

AF:

0.00

AC:

AN:

37894

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24374

East Asian (EAS)

AF:

0.00

AC:

AN:

38294

South Asian (SAS)

AF:

0.00

AC:

AN:

81088

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52658

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5598

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1098924

Other (OTH)

AF:

0.00

AC:

AN:

58850

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000461

AC:

AN:

151928

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74176

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41340

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5158

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68004

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.518

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.:

6728

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Benign

0.78

PhyloP100

1.7

PromoterAI

-0.077

Neutral

(source)

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

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

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over