chr3-108524704-G-A

Variant names:

• chr3-108524704-G-A
• rs2603127
• ENST00000273353.5:c.-58+4559C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000273353.5(MYH15):​c.-58+4559C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.152 in 151,926 control chromosomes in the GnomAD database, including 2,177 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 0.15 (2177 hom., cov: 32)
• Consequence: MYH15 ENST00000273353.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36
• Publications: 10 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]

LOC124909406 (HGNC:):

ACMG classification

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 = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000273353.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH15	ENST00000273353.5	TSL:1	c.-58+4559C>T		intron	N/A	ENSP00000273353.4

Frequencies

GnomAD3 genomes AF: 0.152 AC: 23080 AN: 151808 Hom.: 2175 Cov.: 32

Gnomad AFR AF: 0.0496

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.147

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.00192

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.168

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.181

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

GnomAD4 genome AF: 0.152 AC: 23078 AN: 151926 Hom.: 2177 Cov.: 32 AF XY: 0.148 AC XY: 10990 AN XY: 74250

African (AFR) AF: 0.0495 AC: 2056 AN: 41500

American (AMR) AF: 0.147 AC: 2235 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 767 AN: 3464

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5186

South Asian (SAS) AF: 0.0782 AC: 377 AN: 4820

European-Finnish (FIN) AF: 0.168 AC: 1770 AN: 10566

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15137 AN: 67856

Other (OTH) AF: 0.180 AC: 379 AN: 2102

Alfa AF: 0.196 Hom.: 6911

Bravo AF: 0.148

Asia WGS AF: 0.0440 AC: 157 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.4
DANN	Benign	0.58
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: rs2603127; hg19: chr3-108243551;