Genetic Variant NM_014981.3:c.2399+36G>A (chr3-108453970-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH15	NM_014981.3 link	c.2399+36G>A		intron_variant	Intron 21 of 40	ENST00000693548.1	NP_055796.2	Q9Y2K3
MYH15	XM_011512559.3 link	c.2459+36G>A		intron_variant	Intron 23 of 42		XP_011510861.1	Q9Y2K3

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH15	ENST00000693548.1 link	c.2399+36G>A	intron_variant	Intron 21 of 40		NM_014981.3	ENSP00000508967.1	A0A8I5KXJ3
MYH15	ENST00000273353.5 link	c.2399+36G>A	intron_variant	Intron 22 of 41	1		ENSP00000273353.4	Q9Y2K3
MYH15	ENST00000689784.1 link	c.1418+36G>A	intron_variant	Intron 13 of 32			ENSP00000509841.1	A0A8I5KYE8
MYH15	ENST00000478998.5 link	n.451+36G>A	intron_variant	Intron 4 of 15	2

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

GnomAD3 exomes

AF:

0.674

AC:

165929

AN:

246140

Hom.:

62453

AF XY:

0.684

AC XY:

91317

AN XY:

133450

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 SAS exome

AF:

0.602

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

Gnomad4 AFR exome

AF:

0.713

Gnomad4 AMR exome

AF:

0.482

Gnomad4 ASJ exome

AF:

0.832

Gnomad4 EAS exome

AF:

0.00917

Gnomad4 SAS exome

AF:

0.600

Gnomad4 FIN exome

AF:

0.820

Gnomad4 NFE exome

AF:

0.816

Gnomad4 OTH exome

AF:

0.746

GnomAD4 genome

AF:

0.730

AC:

111034

AN:

152066

Hom.:

42539

Cov.:

AF XY:

0.722

AC XY:

53658

AN XY:

74350

show subpopulations

Gnomad4 AFR

AF:

0.704

Gnomad4 AMR

AF:

0.610

Gnomad4 ASJ

AF:

0.844

Gnomad4 EAS

AF:

0.0182

Gnomad4 SAS

AF:

0.583

Gnomad4 FIN

AF:

0.819

Gnomad4 NFE

AF:

0.815

Gnomad4 OTH

AF:

0.745

Alfa

AF:

0.785

Hom.:

66195

Bravo

AF:

0.710

Asia WGS

AF:

0.355

AC:

1240

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.2

DANN

Benign

0.67

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over