rs2239930

Variant names:

• chr17-10655416-G-A
• rs2239930
• NM_002470.4:c.-8-344C>T

Your query was ambiguous. Multiple possible variants found:

• chr17-10655416-G-A
• chr17-10655416-G-C

Variant summary

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

The NM_002470.4(MYH3):​c.-8-344C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.633 in 152,112 control chromosomes in the GnomAD database, including 32,252 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 0.63 (32252 hom., cov: 33)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.102
• Publications: 9 publications found

Genes affected

MYH3 (HGNC:7573): (myosin heavy chain 3) Myosin is a major contractile protein which converts chemical energy into mechanical energy through the hydrolysis of ATP. Myosin is a hexameric protein composed of a pair of myosin heavy chains (MYH) and two pairs of nonidentical light chains. This gene is a member of the MYH family and encodes a protein with an IQ domain and a myosin head-like domain. Mutations in this gene have been associated with two congenital contracture (arthrogryposis) syndromes, Freeman-Sheldon syndrome and Sheldon-Hall syndrome. [provided by RefSeq, Jul 2008]

MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [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=-0.56).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH3	NM_002470.4	c.-8-344C>T		intron_variant	Intron 2 of 40	ENST00000583535.6	NP_002461.2
MYH3	XM_011523870.4	c.-8-344C>T		intron_variant	Intron 2 of 40		XP_011522172.1
MYH3	XM_011523871.3	c.-8-344C>T		intron_variant	Intron 2 of 40		XP_011522173.1
MYH3	XM_047436127.1	c.-8-344C>T		intron_variant	Intron 4 of 42		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6	c.-8-344C>T		intron_variant	Intron 2 of 40	5	NM_002470.4	ENSP00000464317.1
MYHAS	ENST00000579914.2	n.706-28519G>A		intron_variant	Intron 4 of 4	4
MYH3	ENST00000582580.1	n.81-344C>T		intron_variant	Intron 2 of 3	5
MYHAS	ENST00000584139.2	n.1042-25317G>A		intron_variant	Intron 7 of 8	3

Frequencies

GnomAD3 genomes AF: 0.633 AC: 96181 AN: 151994 Hom.: 32242 Cov.: 33

Gnomad AFR AF: 0.429

Gnomad AMI AF: 0.791

Gnomad AMR AF: 0.589

Gnomad ASJ AF: 0.731

Gnomad EAS AF: 0.368

Gnomad SAS AF: 0.591

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.769

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.633 AC: 96219 AN: 152112 Hom.: 32252 Cov.: 33 AF XY: 0.626 AC XY: 46531 AN XY: 74354

African (AFR) AF: 0.428 AC: 17764 AN: 41484

American (AMR) AF: 0.589 AC: 9010 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.731 AC: 2536 AN: 3468

East Asian (EAS) AF: 0.368 AC: 1900 AN: 5158

South Asian (SAS) AF: 0.591 AC: 2847 AN: 4816

European-Finnish (FIN) AF: 0.720 AC: 7627 AN: 10590

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.769 AC: 52278 AN: 67990

Other (OTH) AF: 0.644 AC: 1361 AN: 2114

Alfa AF: 0.670 Hom.: 5958

Bravo AF: 0.609

Asia WGS AF: 0.498 AC: 1736 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.8
DANN	Benign	0.89
PhyloP100		0.10
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: rs2239930; hg19: chr17-10558733;