chr3-108453970-C-T

Variant names:

• chr3-108453970-C-T
• rs6437783
• NM_014981.3:c.2399+36G>A

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.789
• Publications: 20 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=-0.85).
• 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	c.2399+36G>A		intron_variant	Intron 21 of 40	ENST00000693548.1	NP_055796.2
MYH15	XM_011512559.3	c.2459+36G>A		intron_variant	Intron 23 of 42		XP_011510861.1

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.730 AC: 110978 AN: 151948 Hom.: 42518 Cov.: 31

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

GnomAD2 exomes AF: 0.674 AC: 165929 AN: 246140 AF XY: 0.684

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 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.: 31 AF XY: 0.763 AC XY: 545306 AN XY: 715064

African (AFR) AF: 0.713 AC: 23590 AN: 33086

American (AMR) AF: 0.482 AC: 21369 AN: 44322

Ashkenazi Jewish (ASJ) AF: 0.832 AC: 21316 AN: 25632

East Asian (EAS) AF: 0.00917 AC: 361 AN: 39370

South Asian (SAS) AF: 0.600 AC: 50730 AN: 84496

European-Finnish (FIN) AF: 0.820 AC: 43433 AN: 52948

Middle Eastern (MID) AF: 0.787 AC: 4484 AN: 5694

European-Non Finnish (NFE) AF: 0.816 AC: 894624 AN: 1096488

Other (OTH) AF: 0.746 AC: 44442 AN: 59534

GnomAD4 genome AF: 0.730 AC: 111034 AN: 152066 Hom.: 42539 Cov.: 31 AF XY: 0.722 AC XY: 53658 AN XY: 74350

African (AFR) AF: 0.704 AC: 29195 AN: 41452

American (AMR) AF: 0.610 AC: 9318 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.844 AC: 2928 AN: 3470

East Asian (EAS) AF: 0.0182 AC: 94 AN: 5166

South Asian (SAS) AF: 0.583 AC: 2806 AN: 4816

European-Finnish (FIN) AF: 0.819 AC: 8670 AN: 10590

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55429 AN: 67994

Other (OTH) AF: 0.745 AC: 1569 AN: 2106

Alfa AF: 0.782 Hom.: 82175

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
PhyloP100		-0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6437783; hg19: chr3-108172817; COSMIC: COSV56310341; COSMIC: COSV56310341;