rs4792008

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.4956+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,604,222 control chromosomes in the GnomAD database, including 377,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27810 hom., cov: 33)

Exomes 𝑓: 0.69 ( 349679 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0540

Publications

9 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:

LOC124903927 (HGNC:):

LOC124903927 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=-0.82).

BP6

Variant 17-10632444-G-A is Benign according to our data. Variant chr17-10632444-G-A is described in ClinVar as Benign. ClinVar VariationId is 258690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH3	NM_002470.4 link	c.4956+32C>T		intron_variant	Intron 34 of 40	ENST00000583535.6	NP_002461.2	P11055Q5GJ67

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH3	ENST00000583535.6 link	c.4956+32C>T	intron_variant	Intron 34 of 40	5	NM_002470.4	ENSP00000464317.1	P11055
MYHAS	ENST00000579914.2 link	n.705+18567G>A	intron_variant	Intron 4 of 4	4
MYHAS	ENST00000584139.2 link	n.1041+18567G>A	intron_variant	Intron 7 of 8	3
MYHAS	ENST00000781814.1 link	n.165-2241G>A	intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

87100

AN:

152014

Hom.:

27808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.548

Gnomad NFE

AF:

0.733

Gnomad OTH

AF:

0.589

GnomAD2 exomes

AF:

0.607

AC:

148956

AN:

245230

AF XY:

0.620

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.707

Gnomad EAS exome

AF:

0.362

Gnomad FIN exome

AF:

0.714

Gnomad NFE exome

AF:

0.727

Gnomad OTH exome

AF:

0.652

GnomAD4 exome

AF:

0.686

AC:

995503

AN:

1452090

Hom.:

349679

Cov.:

AF XY:

0.684

AC XY:

494676

AN XY:

722910

show subpopulations

African (AFR)

AF:

0.277

AC:

9241

AN:

33372

American (AMR)

AF:

0.479

AC:

21435

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

18395

AN:

26112

East Asian (EAS)

AF:

0.367

AC:

14568

AN:

39682

South Asian (SAS)

AF:

0.540

AC:

46541

AN:

86142

European-Finnish (FIN)

AF:

0.719

AC:

34287

AN:

47664

Middle Eastern (MID)

AF:

0.563

AC:

2943

AN:

5224

European-Non Finnish (NFE)

AF:

0.729

AC:

808831

AN:

1109004

Other (OTH)

AF:

0.652

AC:

39262

AN:

60184

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

15752

31505

47257

63010

78762

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19642

39284

58926

78568

98210

<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:

0.573

AC:

87125

AN:

152132

Hom.:

27810

Cov.:

AF XY:

0.568

AC XY:

42234

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.295

AC:

12254

AN:

41496

American (AMR)

AF:

0.561

AC:

8581

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

2442

AN:

3472

East Asian (EAS)

AF:

0.371

AC:

1917

AN:

5174

South Asian (SAS)

AF:

0.523

AC:

2524

AN:

4822

European-Finnish (FIN)

AF:

0.706

AC:

7470

AN:

10578

Middle Eastern (MID)

AF:

0.545

AC:

159

AN:

292

European-Non Finnish (NFE)

AF:

0.733

AC:

49855

AN:

67984

Other (OTH)

AF:

0.589

AC:

1245

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1638

3275

4913

6550

8188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

724

1448

2172

2896

3620

<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:

0.653

Hom.:

15053

Bravo

AF:

0.547

Asia WGS

AF:

0.448

AC:

1564

AN:

3478

ClinVar

Significance: 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: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: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

-0.82

CADD

Benign

1.8

(source)

DANN

Benign

0.73

PhyloP100

0.054

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