rs17817203

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_002470.4(MYH3):c.6T>C(p.Ser2Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0204 in 1,613,930 control chromosomes in the GnomAD database, including 359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 35 hom., cov: 32)

Exomes 𝑓: 0.020 ( 324 hom. )

Consequence

MYH3
NM_002470.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -1.02

Publications

5 publications found

Variant links:

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 links:

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]

MYHAS links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.68).

BP6

Variant 17-10655059-A-G is Benign according to our data. Variant chr17-10655059-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.02 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.022 (3348/152132) while in subpopulation AFR AF = 0.031 (1285/41492). AF 95% confidence interval is 0.0296. There are 35 homozygotes in GnomAd4. There are 1604 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 35 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH3	NM_002470.4 link	c.6T>C	p.Ser2Ser	synonymous_variant	Exon 3 of 41	ENST00000583535.6	NP_002461.2	P11055Q5GJ67
MYH3	XM_011523870.4 link	c.6T>C	p.Ser2Ser	synonymous_variant	Exon 3 of 41		XP_011522172.1	P11055
MYH3	XM_011523871.3 link	c.6T>C	p.Ser2Ser	synonymous_variant	Exon 3 of 41		XP_011522173.1	P11055
MYH3	XM_047436127.1 link	c.6T>C	p.Ser2Ser	synonymous_variant	Exon 5 of 43		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH3	ENST00000583535.6 link	c.6T>C	p.Ser2Ser	synonymous_variant	Exon 3 of 41	5	NM_002470.4	ENSP00000464317.1	P11055
MYH3	ENST00000582580.1 link	n.94T>C		non_coding_transcript_exon_variant	Exon 3 of 4	5
MYHAS	ENST00000579914.2 link	n.706-28876A>G		intron_variant	Intron 4 of 4	4
MYHAS	ENST00000584139.2 link	n.1042-25674A>G		intron_variant	Intron 7 of 8	3

Frequencies

GnomAD3 genomes

AF:

0.0220

AC:

3343

AN:

152014

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0310

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00251

Gnomad SAS

AF:

0.0270

Gnomad FIN

AF:

0.0191

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0201

GnomAD2 exomes

AF:

0.0180

AC:

4537

AN:

251470

AF XY:

0.0187

show subpopulations

Gnomad AFR exome

AF:

0.0298

Gnomad AMR exome

AF:

0.00781

Gnomad ASJ exome

AF:

0.00873

Gnomad EAS exome

AF:

0.000870

Gnomad FIN exome

AF:

0.0175

Gnomad NFE exome

AF:

0.0201

Gnomad OTH exome

AF:

0.0184

GnomAD4 exome

AF:

0.0202

AC:

29530

AN:

1461798

Hom.:

324

Cov.:

AF XY:

0.0205

AC XY:

14875

AN XY:

727206

show subpopulations

African (AFR)

AF:

0.0290

AC:

972

AN:

33474

American (AMR)

AF:

0.00780

AC:

349

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00838

AC:

219

AN:

26136

East Asian (EAS)

AF:

0.00589

AC:

234

AN:

39700

South Asian (SAS)

AF:

0.0289

AC:

2489

AN:

86256

European-Finnish (FIN)

AF:

0.0165

AC:

883

AN:

53418

Middle Eastern (MID)

AF:

0.00765

AC:

AN:

5750

European-Non Finnish (NFE)

AF:

0.0209

AC:

23198

AN:

1111946

Other (OTH)

AF:

0.0189

AC:

1142

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1615

3229

4844

6458

8073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

894

1788

2682

3576

4470

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0220

AC:

3348

AN:

152132

Hom.:

Cov.:

AF XY:

0.0216

AC XY:

1604

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.0310

AC:

1285

AN:

41492

American (AMR)

AF:

0.0137

AC:

210

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3470

East Asian (EAS)

AF:

0.00252

AC:

AN:

5166

South Asian (SAS)

AF:

0.0272

AC:

131

AN:

4818

European-Finnish (FIN)

AF:

0.0191

AC:

202

AN:

10574

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0212

AC:

1440

AN:

68010

Other (OTH)

AF:

0.0213

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

174

349

523

698

872

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

132

176

220

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0201

Hom.:

Bravo

AF:

0.0211

Asia WGS

AF:

0.0360

AC:

125

AN:

3478

EpiCase

AF:

0.0208

EpiControl

AF:

0.0181

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Dec 09, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Freeman-Sheldon syndrome

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Distal arthrogryposis type 2B1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.79

(source)

DANN

Benign

0.51

PhyloP100

-1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over