chr17-10670842-C-T

Variant names:

• chr17-10670842-C-T
• rs6503319
• ENST00000579914.2:n.706-13093C>T

Variant summary

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

The ENST00000579914.2(MYHAS):​n.706-13093C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 151,948 control chromosomes in the GnomAD database, including 7,992 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 0.31 (7992 hom., cov: 32)
• Consequence: MYHAS ENST00000579914.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.61
• Publications: 14 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=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.441 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH3	XM_011523870.4	c.-68+7428G>A		intron_variant	Intron 1 of 40		XP_011522172.1
MYH3	XM_047436127.1	c.-3163-2108G>A		intron_variant	Intron 1 of 42		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYHAS	ENST00000579914.2	n.706-13093C>T		intron_variant	Intron 4 of 4	4
MYHAS	ENST00000584139.2	n.1042-9891C>T		intron_variant	Intron 7 of 8	3

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46976 AN: 151830 Hom.: 7963 Cov.: 32

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.212

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.381

Gnomad SAS AF: 0.352

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.306

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

GnomAD4 genome AF: 0.310 AC: 47053 AN: 151948 Hom.: 7992 Cov.: 32 AF XY: 0.306 AC XY: 22753 AN XY: 74268

African (AFR) AF: 0.447 AC: 18503 AN: 41412

American (AMR) AF: 0.211 AC: 3221 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 882 AN: 3466

East Asian (EAS) AF: 0.380 AC: 1965 AN: 5168

South Asian (SAS) AF: 0.352 AC: 1693 AN: 4808

European-Finnish (FIN) AF: 0.200 AC: 2108 AN: 10560

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.260 AC: 17676 AN: 67962

Other (OTH) AF: 0.312 AC: 659 AN: 2114

Alfa AF: 0.277 Hom.: 23809

Bravo AF: 0.316

Asia WGS AF: 0.362 AC: 1260 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.046
DANN	Benign	0.68
PhyloP100		-1.6

Splicing

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

Other links and lift over

dbSNP: rs6503319; hg19: chr17-10574159;