17-10629564-TGG-TGGG

Position:

• chr17-10629564-TGG-TGGG

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_002470.4(MYH3):​c.5796+32dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000902 in 1,567,810 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0010 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00089 (0 hom.)
• Consequence: MYH3 NM_002470.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50

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]

MYH3 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BS2: High AC in GnomAd4 at 157 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH3	NM_002470.4	c.5796+32dupC		intron_variant		ENST00000583535.6	NP_002461.2
MYH3	XM_011523870.4	c.5796+32dupC		intron_variant			XP_011522172.1
MYH3	XM_011523871.3	c.5796+32dupC		intron_variant			XP_011522173.1
MYH3	XM_047436127.1	c.5796+32dupC		intron_variant			XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6	c.5796+32dupC		intron_variant		5	NM_002470.4	ENSP00000464317.1
MYH3	ENST00000577963.1	n.338+32dupC		intron_variant		2
MYH3	ENST00000579928.2	n.326+32dupC		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 156 AN: 151642 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00226

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000263

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000774

Gnomad SAS AF: 0.00479

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000442

Gnomad OTH AF: 0.000960

GnomAD4 exome AF: 0.000888 AC: 1257 AN: 1416056 Hom.: 0 Cov.: 30 AF XY: 0.000951 AC XY: 670 AN XY: 704548

Gnomad4 AFR exome AF: 0.00312

Gnomad4 AMR exome AF: 0.00148

Gnomad4 ASJ exome AF: 0.000276

Gnomad4 EAS exome AF: 0.000882

Gnomad4 SAS exome AF: 0.00365

Gnomad4 FIN exome AF: 0.00116

Gnomad4 NFE exome AF: 0.000576

Gnomad4 OTH exome AF: 0.00114

GnomAD4 genome AF: 0.00103 AC: 157 AN: 151754 Hom.: 0 Cov.: 32 AF XY: 0.00106 AC XY: 79 AN XY: 74212

Gnomad4 AFR AF: 0.00228

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000776

Gnomad4 SAS AF: 0.00479

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000442

Gnomad4 OTH AF: 0.000950

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs147333978; hg19: chr17-10532881;