rs2285467

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002470.4(MYH3):c.349-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,605,336 control chromosomes in the GnomAD database, including 14,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1312 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13416 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.427

Publications

8 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-10651704-T-C is Benign according to our data. Variant chr17-10651704-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 258681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH3	NM_002470.4 link	c.349-36A>G	intron_variant	Intron 4 of 40	ENST00000583535.6	NP_002461.2	P11055Q5GJ67
MYH3	XM_011523870.4 link	c.349-36A>G	intron_variant	Intron 4 of 40		XP_011522172.1	P11055
MYH3	XM_011523871.3 link	c.349-36A>G	intron_variant	Intron 4 of 40		XP_011522173.1	P11055
MYH3	XM_047436127.1 link	c.349-36A>G	intron_variant	Intron 6 of 42		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH3	ENST00000583535.6 link	c.349-36A>G	intron_variant	Intron 4 of 40	5	NM_002470.4	ENSP00000464317.1	P11055
MYH3	ENST00000579489.2 link	n.265A>G	non_coding_transcript_exon_variant	Exon 1 of 4	5
MYHAS	ENST00000579914.2 link	n.706-32231T>C	intron_variant	Intron 4 of 4	4
MYHAS	ENST00000584139.2 link	n.1042-29029T>C	intron_variant	Intron 7 of 8	3

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19448

AN:

151322

Hom.:

1311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.0403

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.122

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.139

GnomAD2 exomes

AF:

0.121

AC:

30290

AN:

250760

AF XY:

0.125

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0693

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0410

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.133

AC:

193256

AN:

1453916

Hom.:

13416

Cov.:

AF XY:

0.134

AC XY:

96943

AN XY:

723818

show subpopulations

African (AFR)

AF:

0.121

AC:

4024

AN:

33298

American (AMR)

AF:

0.0739

AC:

3302

AN:

44686

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

3683

AN:

26058

East Asian (EAS)

AF:

0.0362

AC:

1437

AN:

39654

South Asian (SAS)

AF:

0.133

AC:

11482

AN:

86124

European-Finnish (FIN)

AF:

0.131

AC:

7010

AN:

53360

Middle Eastern (MID)

AF:

0.148

AC:

849

AN:

5746

European-Non Finnish (NFE)

AF:

0.139

AC:

153330

AN:

1104874

Other (OTH)

AF:

0.135

AC:

8139

AN:

60116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

9633

19265

28898

38530

48163

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5430

10860

16290

21720

27150

<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:

0.128

AC:

19446

AN:

151420

Hom.:

1312

Cov.:

AF XY:

0.128

AC XY:

9439

AN XY:

73894

show subpopulations

African (AFR)

AF:

0.122

AC:

5054

AN:

41260

American (AMR)

AF:

0.114

AC:

1735

AN:

15210

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

471

AN:

3468

East Asian (EAS)

AF:

0.0408

AC:

210

AN:

5148

South Asian (SAS)

AF:

0.129

AC:

620

AN:

4792

European-Finnish (FIN)

AF:

0.129

AC:

1328

AN:

10318

Middle Eastern (MID)

AF:

0.110

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.141

AC:

9578

AN:

67932

Other (OTH)

AF:

0.137

AC:

287

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

822

1644

2467

3289

4111

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

224

448

672

896

1120

<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:

0.134

Hom.:

340

Bravo

AF:

0.125

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Freeman-Sheldon syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Contractures, pterygia, and variable skeletal fusions syndrome 1B

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Arthrogryposis, distal, type 2B3

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A

Benign:1

Sep 05, 2021

Genome-Nilou Lab

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

-0.86

CADD

Benign

2.7

(source)

DANN

Benign

0.24

PhyloP100

0.43

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

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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