Genetic Variant MYH15:c.2399+36G>A (chr3-108453970-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_014981.3(MYH15):c.2399+36G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.763 in 1,593,636 control chromosomes in the GnomAD database, including 482,840 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.73 ( 42539 hom., cov: 31)

Exomes 𝑓: 0.77 ( 440301 hom. )

Consequence

MYH15
NM_014981.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.789

Publications

20 publications found

Variant links:

Genes affected

MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

MYH15 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_014981.3, 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

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.81 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014981.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH15	NM_014981.3	MANE Select	c.2399+36G>A		intron	N/A	NP_055796.2	A0A8I5KXJ3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MYH15	ENST00000693548.1	MANE Select	c.2399+36G>A	intron	N/A	ENSP00000508967.1	Q9Y2K3
MYH15	ENST00000273353.5	TSL:1	c.2399+36G>A	intron	N/A	ENSP00000273353.4	Q9Y2K3
MYH15	ENST00000689784.1		c.1418+36G>A	intron	N/A	ENSP00000509841.1	A0A8I5KYE8

Frequencies

GnomAD3 genomes

AF:

0.730

AC:

110978

AN:

151948

Hom.:

42518

Cov.:

show subpopulations

Gnomad AFR

AF:

0.704

Gnomad AMI

AF:

0.870

Gnomad AMR

AF:

0.612

Gnomad ASJ

AF:

0.844

Gnomad EAS

AF:

0.0185

Gnomad SAS

AF:

0.583

Gnomad FIN

AF:

0.819

Gnomad MID

AF:

0.797

Gnomad NFE

AF:

0.815

Gnomad OTH

AF:

0.747

GnomAD2 exomes

AF:

0.674

AC:

165929

AN:

246140

AF XY:

0.684

show subpopulations

Gnomad AFR exome

AF:

0.708

Gnomad AMR exome

AF:

0.459

Gnomad ASJ exome

AF:

0.836

Gnomad EAS exome

AF:

0.0132

Gnomad FIN exome

AF:

0.819

Gnomad NFE exome

AF:

0.815

Gnomad OTH exome

AF:

0.740

GnomAD4 exome

AF:

0.766

AC:

1104349

AN:

1441570

Hom.:

440301

Cov.:

AF XY:

0.763

AC XY:

545306

AN XY:

715064

show subpopulations

African (AFR)

AF:

0.713

AC:

23590

AN:

33086

American (AMR)

AF:

0.482

AC:

21369

AN:

44322

Ashkenazi Jewish (ASJ)

AF:

0.832

AC:

21316

AN:

25632

East Asian (EAS)

AF:

0.00917

AC:

361

AN:

39370

South Asian (SAS)

AF:

0.600

AC:

50730

AN:

84496

European-Finnish (FIN)

AF:

0.820

AC:

43433

AN:

52948

Middle Eastern (MID)

AF:

0.787

AC:

4484

AN:

5694

European-Non Finnish (NFE)

AF:

0.816

AC:

894624

AN:

1096488

Other (OTH)

AF:

0.746

AC:

44442

AN:

59534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.479

Heterozygous variant carriers

9994

19987

29981

39974

49968

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20400

40800

61200

81600

102000

<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:

0.730

AC:

111034

AN:

152066

Hom.:

42539

Cov.:

AF XY:

0.722

AC XY:

53658

AN XY:

74350

show subpopulations

African (AFR)

AF:

0.704

AC:

29195

AN:

41452

American (AMR)

AF:

0.610

AC:

9318

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.844

AC:

2928

AN:

3470

East Asian (EAS)

AF:

0.0182

AC:

AN:

5166

South Asian (SAS)

AF:

0.583

AC:

2806

AN:

4816

European-Finnish (FIN)

AF:

0.819

AC:

8670

AN:

10590

Middle Eastern (MID)

AF:

0.789

AC:

232

AN:

294

European-Non Finnish (NFE)

AF:

0.815

AC:

55429

AN:

67994

Other (OTH)

AF:

0.745

AC:

1569

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1337

2673

4010

5346

6683

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

816

1632

2448

3264

4080

<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:

0.782

Hom.:

82175

Bravo

AF:

0.710

Asia WGS

AF:

0.355

AC:

1240

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

(source)

DANN

Benign

0.67

PhyloP100

-0.79

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