rs2239930

chr17-10655416-G-Achr17-10655416-G-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
MYH3	NM_002470.4	c.-8-344C>T		intron_variant		ENST00000583535.6
MYH3	XM_011523870.4	c.-8-344C>T		intron_variant
MYH3	XM_011523871.3	c.-8-344C>T		intron_variant
MYH3	XM_047436127.1	c.-8-344C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH3	ENST00000583535.6	c.-8-344C>T		intron_variant		5	NM_002470.4	P1
MYH3	ENST00000582580.1	n.81-344C>T		intron_variant, non_coding_transcript_variant		5

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

Gnomad4 AFR AF: 0.428

Gnomad4 AMR AF: 0.589

Gnomad4 ASJ AF: 0.731

Gnomad4 EAS AF: 0.368

Gnomad4 SAS AF: 0.591

Gnomad4 FIN AF: 0.720

Gnomad4 NFE AF: 0.769

Gnomad4 OTH AF: 0.644

Alfa AF: 0.677 Hom.: 5891

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

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: rs2239930; hg19: chr17-10558733;