rs169313

Variant names:

• chr17-10664166-A-C
• rs169313
• ENST00000579914.2:n.706-19769A>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

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

The ENST00000579914.2(MYHAS):​n.706-19769A>C 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: MYHAS ENST00000579914.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 2 publications found

Genes affected

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]

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 Gene-Disease associations (from GenCC):

• Freeman-Sheldon syndrome

  Inheritance: AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Ambry Genetics
• distal arthrogryposis type 2B1

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• contractures, pterygia, and variable skeletal fusions syndrome 1B

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• digitotalar dysmorphism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Sheldon-hall syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive multiple pterygium syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spondylocarpotarsal synostosis syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
MYH3	XM_011523870.4	c.-67-8018T>G		intron_variant	Intron 1 of 40		XP_011522172.1
MYH3	XM_047436127.1	c.-3047-3898T>G		intron_variant	Intron 2 of 42		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYHAS	ENST00000579914.2	n.706-19769A>C		intron_variant	Intron 4 of 4	4
MYHAS	ENST00000584139.2	n.1042-16567A>C		intron_variant	Intron 7 of 8	3

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

African (AFR) AF: 0.830 AC: 34388 AN: 41418

American (AMR) AF: 0.571 AC: 8697 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1584 AN: 3470

East Asian (EAS) AF: 0.719 AC: 3712 AN: 5166

South Asian (SAS) AF: 0.604 AC: 2891 AN: 4788

European-Finnish (FIN) AF: 0.434 AC: 4559 AN: 10494

Middle Eastern (MID) AF: 0.555 AC: 162 AN: 292

European-Non Finnish (NFE) AF: 0.430 AC: 29213 AN: 67880

Other (OTH) AF: 0.547 AC: 1147 AN: 2096

Alfa AF: 0.482 Hom.: 13714

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
PhyloP100		-1.4

Splicing

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

Other links and lift over

dbSNP: rs169313; hg19: chr17-10567483;