rs2227294

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.307+37A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 1,609,092 control chromosomes in the GnomAD database, including 48,643 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). The gene MYL3 is included in the ClinGen Criteria Specification Registry.

Frequency

Genomes: 𝑓 0.34 ( 14755 hom., cov: 32)

Exomes 𝑓: 0.17 ( 33888 hom. )

Consequence

MYL3
NM_000258.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.260

Publications

9 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: Labcorp Genetics (formerly Invitae), G2P, 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

new If you want to explore the variant's impact on the transcript NM_000258.3, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Specifications for MYL3 are available in the ClinGen Criteria Specification Registry and recommended for reference when assigning criteria.

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 3-46860639-T-G is Benign according to our data. Variant chr3-46860639-T-G is described in ClinVar as Benign. ClinVar VariationId is 255638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000258.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYL3	NM_000258.3	MANE Select	c.307+37A>C	intron	N/A	NP_000249.1	P08590
MYL3	NM_001406937.1		c.307+37A>C	intron	N/A	NP_001393866.1	P08590
MYL3	NM_001406938.1		c.307+37A>C	intron	N/A	NP_001393867.1	P08590

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYL3	ENST00000292327.6	TSL:1 MANE Select	c.307+37A>C	intron	N/A	ENSP00000292327.4	P08590
MYL3	ENST00000395869.5	TSL:1	c.307+37A>C	intron	N/A	ENSP00000379210.1	P08590
MYL3	ENST00000713934.1		c.439+37A>C	intron	N/A	ENSP00000519231.1	A0AAQ5BH63

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

51348

AN:

151966

Hom.:

14710

Cov.:

show subpopulations

Gnomad AFR

AF:

0.774

Gnomad AMI

AF:

0.198

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.226

Gnomad EAS

AF:

0.375

Gnomad SAS

AF:

0.411

Gnomad FIN

AF:

0.140

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.300

GnomAD2 exomes

AF:

0.253

AC:

62292

AN:

246266

AF XY:

0.245

show subpopulations

Gnomad AFR exome

AF:

0.785

Gnomad AMR exome

AF:

0.323

Gnomad ASJ exome

AF:

0.231

Gnomad EAS exome

AF:

0.379

Gnomad FIN exome

AF:

0.138

Gnomad NFE exome

AF:

0.120

Gnomad OTH exome

AF:

0.199

GnomAD4 exome

AF:

0.170

AC:

247368

AN:

1457008

Hom.:

33888

Cov.:

AF XY:

0.174

AC XY:

126456

AN XY:

724998

show subpopulations

African (AFR)

AF:

0.799

AC:

26715

AN:

33450

American (AMR)

AF:

0.318

AC:

14201

AN:

44654

Ashkenazi Jewish (ASJ)

AF:

0.229

AC:

5972

AN:

26122

East Asian (EAS)

AF:

0.376

AC:

14916

AN:

39682

South Asian (SAS)

AF:

0.400

AC:

34443

AN:

86186

European-Finnish (FIN)

AF:

0.134

AC:

6675

AN:

49740

Middle Eastern (MID)

AF:

0.285

AC:

1482

AN:

5200

European-Non Finnish (NFE)

AF:

0.117

AC:

130149

AN:

1111692

Other (OTH)

AF:

0.213

AC:

12815

AN:

60282

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

10040

20080

30120

40160

50200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5424

10848

16272

21696

27120

<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:

0.338

AC:

51450

AN:

152084

Hom.:

14755

Cov.:

AF XY:

0.340

AC XY:

25311

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.775

AC:

32126

AN:

41468

American (AMR)

AF:

0.271

AC:

4142

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.226

AC:

784

AN:

3462

East Asian (EAS)

AF:

0.375

AC:

1937

AN:

5164

South Asian (SAS)

AF:

0.411

AC:

1976

AN:

4812

European-Finnish (FIN)

AF:

0.140

AC:

1486

AN:

10598

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8100

AN:

67974

Other (OTH)

AF:

0.299

AC:

630

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1136

2272

3409

4545

5681

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

440

880

1320

1760

2200

<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:

0.182

Hom.:

10617

Bravo

AF:

0.368

Asia WGS

AF:

0.371

AC:

1288

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Hypertrophic cardiomyopathy 8 (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

3.6

(source)

DANN

Benign

0.33

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

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