NM_000258.3:c.411G>T

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_000258.3(MYL3):​c.411G>T​(p.Leu137Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000477 in 1,614,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L137L) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )

Consequence

MYL3
NM_000258.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.143

Publications

1 publications found
Variant links:
Genes affected
MYL3 (HGNC:7584): (myosin light chain 3) MYL3 encodes myosin light chain 3, an alkali light chain also referred to in the literature as both the ventricular isoform and the slow skeletal muscle isoform. Mutations in MYL3 have been identified as a cause of mid-left ventricular chamber type hypertrophic cardiomyopathy. [provided by RefSeq, Jul 2008]
MYL3 Gene-Disease associations (from GenCC):
  • hypertrophic cardiomyopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • hypertrophic cardiomyopathy 8
    Inheritance: AD, SD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • arrhythmogenic right ventricular cardiomyopathy
    Inheritance: AD Classification: LIMITED Submitted by: ClinGen
  • dilated cardiomyopathy
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -15 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
Variant 3-46859545-C-A is Benign according to our data. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-A is described in CliVar as Benign/Likely_benign. Clinvar id is 518858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=0.143 with no splicing effect.
BS2
High AC in GnomAd4 at 13 AD,SD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MYL3NM_000258.3 linkc.411G>T p.Leu137Leu synonymous_variant Exon 4 of 7 ENST00000292327.6 NP_000249.1 P08590A0A024R2Q5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MYL3ENST00000292327.6 linkc.411G>T p.Leu137Leu synonymous_variant Exon 4 of 7 1 NM_000258.3 ENSP00000292327.4 P08590

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152244
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00173
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00143
GnomAD2 exomes
AF:
0.000139
AC:
35
AN:
251486
AF XY:
0.000132
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00190
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000438
AC:
64
AN:
1461886
Hom.:
0
Cov.:
32
AF XY:
0.0000385
AC XY:
28
AN XY:
727246
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33480
American (AMR)
AF:
0.00
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26136
East Asian (EAS)
AF:
0.00103
AC:
41
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86256
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1112008
Other (OTH)
AF:
0.000381
AC:
23
AN:
60394
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.493
Heterozygous variant carriers
0
4
8
11
15
19
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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:
0.0000853
AC:
13
AN:
152362
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74512
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41582
American (AMR)
AF:
0.00
AC:
0
AN:
15308
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00174
AC:
9
AN:
5180
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4830
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10626
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
0.0000147
AC:
1
AN:
68044
Other (OTH)
AF:
0.00142
AC:
3
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
2
3
4
5
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<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.:
0
Bravo
AF:
0.0000982

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Cardiomyopathy Benign:2
Aug 23, 2016
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Oct 08, 2018
Color Diagnostics, LLC DBA Color Health
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy Benign:2
Jan 21, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Jan 11, 2024
All of Us Research Program, National Institutes of Health
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
Apr 09, 2025
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not provided Benign:1
Mar 03, 2015
GeneDx
Significance:Benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Cardiovascular phenotype Benign:1
Jul 12, 2017
Ambry Genetics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
CADD
Benign
6.9
DANN
Benign
0.70
PhyloP100
0.14
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs2233265; hg19: chr3-46901035; API