rs169313

Positions:

• chr17-10664166-A-C
• chr17-10664166-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_011523870.4(MYH3):​c.-67-8018T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,754 control chromosomes in the GnomAD database, including 27,076 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 0.57 (27076 hom., cov: 31)
• Consequence: MYH3 XM_011523870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.823 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH3	XM_011523870.4	c.-67-8018T>G		intron_variant			XP_011522172.1
MYH3	XM_047436127.1	c.-3047-3898T>G		intron_variant			XP_047292083.1
		n.10664166A>C		intergenic_region

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86535 AN: 151638 Hom.: 27038 Cov.: 31

Gnomad AFR AF: 0.830

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.571

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.719

Gnomad SAS AF: 0.605

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.430

Gnomad OTH AF: 0.549

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

GnomAD4 genome AF: 0.571 AC: 86621 AN: 151754 Hom.: 27076 Cov.: 31 AF XY: 0.575 AC XY: 42660 AN XY: 74170

Gnomad4 AFR AF: 0.830

Gnomad4 AMR AF: 0.571

Gnomad4 ASJ AF: 0.456

Gnomad4 EAS AF: 0.719

Gnomad4 SAS AF: 0.604

Gnomad4 FIN AF: 0.434

Gnomad4 NFE AF: 0.430

Gnomad4 OTH AF: 0.547

Alfa AF: 0.456 Hom.: 5848

Bravo AF: 0.591

Asia WGS AF: 0.670 AC: 2325 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.077
DANN	Benign	0.33

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs169313; hg19: chr17-10567483;