rs3996018

Positions:

• chr3-108444355-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014981.3(MYH15):​c.2655+285C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.787 in 151,866 control chromosomes in the GnomAD database, including 47,323 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 0.79 (47323 hom., cov: 28)
• Consequence: MYH15 NM_014981.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.837 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH15	NM_014981.3	c.2655+285C>G		intron_variant		ENST00000693548.1	NP_055796.2
MYH15	XM_011512559.3	c.2715+285C>G		intron_variant			XP_011510861.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH15	ENST00000693548.1	c.2655+285C>G		intron_variant			NM_014981.3	ENSP00000508967.1
MYH15	ENST00000273353.5	c.2655+285C>G		intron_variant		1		ENSP00000273353.4
MYH15	ENST00000689784.1	c.1674+285C>G		intron_variant				ENSP00000509841.1
MYH15	ENST00000478998.5	n.707+285C>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119457 AN: 151748 Hom.: 47271 Cov.: 28

Gnomad AFR AF: 0.845

Gnomad AMI AF: 0.895

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.587

Gnomad SAS AF: 0.699

Gnomad FIN AF: 0.773

Gnomad MID AF: 0.771

Gnomad NFE AF: 0.785

Gnomad OTH AF: 0.777

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.787 AC: 119559 AN: 151866 Hom.: 47323 Cov.: 28 AF XY: 0.784 AC XY: 58132 AN XY: 74188

Gnomad4 AFR AF: 0.845

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.763

Gnomad4 EAS AF: 0.586

Gnomad4 SAS AF: 0.698

Gnomad4 FIN AF: 0.773

Gnomad4 NFE AF: 0.785

Gnomad4 OTH AF: 0.778

Alfa AF: 0.791 Hom.: 5940

Bravo AF: 0.788

Asia WGS AF: 0.678 AC: 2359 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.58
DANN	Benign	0.60

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

LitVar

Other links and lift over

dbSNP: rs3996018; hg19: chr3-108163202;