rs936175

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000258.3(MYL3):c.129+44G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 1,612,216 control chromosomes in the GnomAD database, including 39,244 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 11679 hom., cov: 32)

Exomes 𝑓: 0.16 ( 27565 hom. )

Consequence

MYL3
NM_000258.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0150

Publications

5 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 3-46863218-C-A is Benign according to our data. Variant chr3-46863218-C-A is described in ClinVar as Benign. ClinVar VariationId is 255637.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.686 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYL3	NM_000258.3 link	c.129+44G>T	intron_variant	Intron 1 of 6	ENST00000292327.6	NP_000249.1	P08590A0A024R2Q5
MYL3	NM_001406937.1 link	c.129+44G>T	intron_variant	Intron 1 of 5		NP_001393866.1
MYL3	NM_001406938.1 link	c.129+44G>T	intron_variant	Intron 3 of 8		NP_001393867.1
MYL3	NM_001406939.1 link	c.129+44G>T	intron_variant	Intron 3 of 8		NP_001393868.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYL3	ENST00000292327.6 link	c.129+44G>T		intron_variant	Intron 1 of 6	1	NM_000258.3	ENSP00000292327.4		P08590

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45577

AN:

152054

Hom.:

11646

Cov.:

show subpopulations

Gnomad AFR

AF:

0.692

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.175

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.238

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.285

Gnomad NFE

AF:

0.118

Gnomad OTH

AF:

0.275

GnomAD2 exomes

AF:

0.207

AC:

51676

AN:

249054

AF XY:

0.209

show subpopulations

Gnomad AFR exome

AF:

0.696

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.230

Gnomad EAS exome

AF:

0.231

Gnomad FIN exome

AF:

0.137

Gnomad NFE exome

AF:

0.119

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.157

AC:

228752

AN:

1460044

Hom.:

27565

Cov.:

AF XY:

0.163

AC XY:

118089

AN XY:

726378

show subpopulations

African (AFR)

AF:

0.714

AC:

23888

AN:

33440

American (AMR)

AF:

0.137

AC:

6115

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.228

AC:

5958

AN:

26108

East Asian (EAS)

AF:

0.231

AC:

9175

AN:

39652

South Asian (SAS)

AF:

0.395

AC:

34041

AN:

86172

European-Finnish (FIN)

AF:

0.134

AC:

7124

AN:

53134

Middle Eastern (MID)

AF:

0.270

AC:

1410

AN:

5222

European-Non Finnish (NFE)

AF:

0.116

AC:

129130

AN:

1111324

Other (OTH)

AF:

0.198

AC:

11911

AN:

60290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

9118

18237

27355

36474

45592

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5226

10452

15678

20904

26130

<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:

0.300

AC:

45660

AN:

152172

Hom.:

11679

Cov.:

AF XY:

0.301

AC XY:

22423

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.692

AC:

28699

AN:

41460

American (AMR)

AF:

0.175

AC:

2669

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

785

AN:

3472

East Asian (EAS)

AF:

0.238

AC:

1232

AN:

5176

South Asian (SAS)

AF:

0.402

AC:

1941

AN:

4830

European-Finnish (FIN)

AF:

0.140

AC:

1481

AN:

10612

Middle Eastern (MID)

AF:

0.289

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.118

AC:

8009

AN:

68014

Other (OTH)

AF:

0.274

AC:

578

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1175

2349

3524

4698

5873

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.176

Hom.:

2632

Bravo

AF:

0.317

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy 8

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

2.4

(source)

DANN

Benign

0.66

PhyloP100

0.015

PromoterAI

-0.016

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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