rs3996018

Variant names:

• chr3-108444355-G-C
• rs3996018
• NM_014981.3:c.2655+285C>G

Variant summary

Our verdict is Benign. The variant received -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. Variant has been reported in ClinVar as (no stars).

• 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
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

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.2655+285C>G		intron	N/A	NP_055796.2	A0A8I5KXJ3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH15	ENST00000693548.1	MANE Select	c.2655+285C>G		intron	N/A	ENSP00000508967.1	Q9Y2K3
	MYH15	ENST00000273353.5	TSL:1	c.2655+285C>G		intron	N/A	ENSP00000273353.4	Q9Y2K3
	MYH15	ENST00000689784.1		c.1674+285C>G		intron	N/A	ENSP00000509841.1	A0A8I5KYE8

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

African (AFR) AF: 0.845 AC: 34991 AN: 41414

American (AMR) AF: 0.748 AC: 11408 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2644 AN: 3464

East Asian (EAS) AF: 0.586 AC: 3014 AN: 5146

South Asian (SAS) AF: 0.698 AC: 3350 AN: 4798

European-Finnish (FIN) AF: 0.773 AC: 8138 AN: 10534

Middle Eastern (MID) AF: 0.771 AC: 225 AN: 292

European-Non Finnish (NFE) AF: 0.785 AC: 53330 AN: 67946

Other (OTH) AF: 0.778 AC: 1643 AN: 2112

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.58
DANN	Benign	0.60
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3996018; hg19: chr3-108163202;