rs147333978

Positions:

• chr17-10629564-TGG-T
• chr17-10629564-TGG-TG
• 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+31_5796+32del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000804 in 1,580,522 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00017 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000071 (2 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]

ACMG classification

Verdict is Likely_benign. Variant got -1 ACMG points.

• BS2: High AC in GnomAd4 at 26 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+31_5796+32del		intron_variant		ENST00000583535.6	NP_002461.2
MYH3	XM_011523870.4	c.5796+31_5796+32del		intron_variant			XP_011522172.1
MYH3	XM_011523871.3	c.5796+31_5796+32del		intron_variant			XP_011522173.1
MYH3	XM_047436127.1	c.5796+31_5796+32del		intron_variant			XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6	c.5796+31_5796+32del		intron_variant		5	NM_002470.4	ENSP00000464317	P1
MYH3	ENST00000577963.1	n.338+31_338+32del		intron_variant, non_coding_transcript_variant		2
MYH3	ENST00000579928.2	n.326+31_326+32del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.000119 AC: 18 AN: 151664 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00290

Gnomad SAS AF: 0.000416

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000480

GnomAD3 exomes AF: 0.000114 AC: 27 AN: 237438 Hom.: 0 AF XY: 0.000109 AC XY: 14 AN XY: 128690

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00111

Gnomad SAS exome AF: 0.000287

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000707 AC: 101 AN: 1428746 Hom.: 2 AF XY: 0.0000731 AC XY: 52 AN XY: 710904

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000733

Gnomad4 SAS exome AF: 0.000464

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000183

Gnomad4 OTH exome AF: 0.000545

GnomAD4 genome AF: 0.000171 AC: 26 AN: 151776 Hom.: 1 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74222

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00291

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00427

Bravo AF: 0.0000907

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;