rs3843872

Positions:

• chr3-108510275-C-G
• chr3-108510275-C-T

Variant summary

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

The NM_014981.3(MYH15):​c.88+168G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,072 control chromosomes in the GnomAD database, including 4,558 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 0.23 (4558 hom., cov: 31)
• Consequence: MYH15 NM_014981.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.546

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH15	NM_014981.3	c.88+168G>C		intron_variant		ENST00000693548.1
MYH15	XM_011512559.3	c.148+168G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH15	ENST00000693548.1	c.88+168G>C		intron_variant			NM_014981.3	P1
MYH15	ENST00000273353.5	c.88+168G>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34317 AN: 151954 Hom.: 4558 Cov.: 31

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.227

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.00770

Gnomad SAS AF: 0.179

Gnomad FIN AF: 0.278

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.226 AC: 34320 AN: 152072 Hom.: 4558 Cov.: 31 AF XY: 0.223 AC XY: 16543 AN XY: 74346

Gnomad4 AFR AF: 0.126

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.222

Gnomad4 EAS AF: 0.00753

Gnomad4 SAS AF: 0.180

Gnomad4 FIN AF: 0.278

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.231

Alfa AF: 0.250 Hom.: 656

Bravo AF: 0.214

Asia WGS AF: 0.121 AC: 424 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.1
DANN	Benign	0.67

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: rs3843872; hg19: chr3-108229122;