3-46863355-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_000258.3(MYL3):c.36T>C(p.Asp12Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000787 in 1,613,786 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 (★★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

MYL3
NM_000258.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -5.11

Publications

0 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

MYL3 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 3-46863355-A-G is Benign according to our data. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46863355-A-G is described in CliVar as Likely_benign. Clinvar id is 378219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-5.11 with no splicing effect.

BS2

High AC in GnomAd4 at 7 AD,SD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL3	NM_000258.3 link	c.36T>C	p.Asp12Asp	synonymous_variant	Exon 1 of 7	ENST00000292327.6	NP_000249.1	P08590A0A024R2Q5
MYL3	NM_001406937.1 link	c.36T>C	p.Asp12Asp	synonymous_variant	Exon 1 of 6		NP_001393866.1
MYL3	NM_001406938.1 link	c.36T>C	p.Asp12Asp	synonymous_variant	Exon 3 of 9		NP_001393867.1
MYL3	NM_001406939.1 link	c.36T>C	p.Asp12Asp	synonymous_variant	Exon 3 of 9		NP_001393868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL3	ENST00000292327.6 link	c.36T>C	p.Asp12Asp	synonymous_variant	Exon 1 of 7	1	NM_000258.3	ENSP00000292327.4		P08590

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152206

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000279

AC:

AN:

251100

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000821

AC:

120

AN:

1461580

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33478

American (AMR)

AF:

0.00

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26130

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53146

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000105

AC:

117

AN:

1111996

Other (OTH)

AF:

0.0000331

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

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:

0.0000460

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000672

AC XY:

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41462

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

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:

0.0000678

Hom.:

Bravo

AF:

0.0000453

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Cardiomyopathy

Benign:2

May 24, 2017

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2019

Color Diagnostics, LLC DBA Color Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy

Benign:2

Jan 31, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 18, 2023

All of Us Research Program, National Institutes of Health

Significance:Likely 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:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BP6;BP7 -

MYL3-related disorder

Benign:1

Aug 17, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

not provided

Benign:1

Mar 27, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

May 31, 2018

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

-0.83

CADD

Benign

0.067

(source)

DANN

Benign

0.48

PhyloP100

-5.1

PromoterAI

0.047

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over