3-46859545-C-T

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.411G>A(p.Leu137Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,130 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 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

MYL3
NM_000258.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

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

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=-0.47).

BP6

Variant 3-46859545-C-T is Benign according to our data. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-46859545-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 701416.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 GnomAdExome4 at 23 AD,SD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYL3	NM_000258.3 link	c.411G>A	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
MYL3	ENST00000292327.6 link	c.411G>A	p.Leu137Leu	synonymous_variant	Exon 4 of 7	1	NM_000258.3	ENSP00000292327.4		P08590

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00

GnomAD2 exomes

AF:

0.0000795

AC:

AN:

251486

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000157

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.000514

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1112008

Other (OTH)

AF:

0.00

AC:

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.521

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:

0.00000657

AC:

AN:

152244

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74384

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41460

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5192

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68052

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

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.:

Bravo

AF:

0.0000491

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hypertrophic cardiomyopathy

Benign:2

Dec 18, 2023

All of Us Research Program, National Institutes of Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 03, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiomyopathy

Benign:1

May 27, 2022

Color Diagnostics, LLC DBA Color Health

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Feb 17, 2024

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

-0.47

CADD

Benign

7.5

(source)

DANN

Benign

0.74

PhyloP100

0.14

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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