NM_002470.4:c.1141+32G>A

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.1141+32G>A 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 1,610,474 control chromosomes in the GnomAD database, including 378,920 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27738 hom., cov: 29)

Exomes 𝑓: 0.69 ( 351182 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.772

Publications

6 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=-0.89).

BP6

Variant 17-10645675-C-T is Benign according to our data. Variant chr17-10645675-C-T is described in ClinVar as Benign. ClinVar VariationId is 258668.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	Effect	Exon rank	MANE	Protein	UniProt
MYH3	NM_002470.4 link	c.1141+32G>A	intron_variant	Intron 12 of 40	ENST00000583535.6	NP_002461.2	P11055Q5GJ67
MYH3	XM_011523870.4 link	c.1141+32G>A	intron_variant	Intron 12 of 40		XP_011522172.1	P11055
MYH3	XM_011523871.3 link	c.1141+32G>A	intron_variant	Intron 12 of 40		XP_011522173.1	P11055
MYH3	XM_047436127.1 link	c.1141+32G>A	intron_variant	Intron 14 of 42		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH3	ENST00000583535.6 link	c.1141+32G>A	intron_variant	Intron 12 of 40	5	NM_002470.4	ENSP00000464317.1	P11055
MYHAS	ENST00000579914.2 link	n.705+31798C>T	intron_variant	Intron 4 of 4	4
MYHAS	ENST00000584139.2 link	n.1041+31798C>T	intron_variant	Intron 7 of 8	3

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

86810

AN:

151434

Hom.:

27736

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.357

Gnomad SAS

AF:

0.526

Gnomad FIN

AF:

0.710

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.734

Gnomad OTH

AF:

0.593

GnomAD2 exomes

AF:

0.609

AC:

152648

AN:

250764

AF XY:

0.621

show subpopulations

Gnomad AFR exome

AF:

0.293

Gnomad AMR exome

AF:

0.466

Gnomad ASJ exome

AF:

0.706

Gnomad EAS exome

AF:

0.348

Gnomad FIN exome

AF:

0.715

Gnomad NFE exome

AF:

0.727

Gnomad OTH exome

AF:

0.652

GnomAD4 exome

AF:

0.685

AC:

999540

AN:

1458922

Hom.:

351182

Cov.:

AF XY:

0.684

AC XY:

496400

AN XY:

725866

show subpopulations

African (AFR)

AF:

0.276

AC:

9210

AN:

33398

American (AMR)

AF:

0.479

AC:

21416

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.704

AC:

18382

AN:

26126

East Asian (EAS)

AF:

0.344

AC:

13644

AN:

39686

South Asian (SAS)

AF:

0.540

AC:

46557

AN:

86158

European-Finnish (FIN)

AF:

0.720

AC:

38256

AN:

53106

Middle Eastern (MID)

AF:

0.580

AC:

2450

AN:

4224

European-Non Finnish (NFE)

AF:

0.729

AC:

810439

AN:

1111340

Other (OTH)

AF:

0.651

AC:

39186

AN:

60182

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

16252

32504

48755

65007

81259

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19682

39364

59046

78728

98410

<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:

86833

AN:

151552

Hom.:

27738

Cov.:

AF XY:

0.569

AC XY:

42065

AN XY:

73970

show subpopulations

African (AFR)

AF:

0.295

AC:

12179

AN:

41352

American (AMR)

AF:

0.561

AC:

8542

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.703

AC:

2438

AN:

3470

East Asian (EAS)

AF:

0.358

AC:

1780

AN:

4976

South Asian (SAS)

AF:

0.526

AC:

2520

AN:

4792

European-Finnish (FIN)

AF:

0.710

AC:

7456

AN:

10502

Middle Eastern (MID)

AF:

0.544

AC:

160

AN:

294

European-Non Finnish (NFE)

AF:

0.734

AC:

49841

AN:

67926

Other (OTH)

AF:

0.593

AC:

1241

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

1567

3134

4702

6269

7836

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.675

Hom.:

47652

Bravo

AF:

0.546

Asia WGS

AF:

0.442

AC:

1541

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

-0.89

CADD

Benign

2.2

(source)

DANN

Benign

0.55

PhyloP100

-0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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