rs34693726

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_002472.3(MYH8):c.1907C>T(p.Ala636Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0576 in 1,613,654 control chromosomes in the GnomAD database, including 3,088 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A636S) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.054 ( 248 hom., cov: 33)

Exomes 𝑓: 0.058 ( 2840 hom. )

Consequence

MYH8
NM_002472.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.49

Publications

14 publications found

Variant links:

Genes affected

MYH8 (HGNC:7578): (myosin heavy chain 8) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]

MYH8 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 (MetaRNN=0.0019810796).

BP6

Variant 17-10409155-G-A is Benign according to our data. Variant chr17-10409155-G-A is described in ClinVar as Benign. ClinVar VariationId is 129671.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002472.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYH8	NM_002472.3	MANE Select	c.1907C>T	p.Ala636Val	missense	Exon 17 of 40	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.167+2917G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYH8	ENST00000403437.2	TSL:5 MANE Select	c.1907C>T	p.Ala636Val	missense	Exon 17 of 40	ENSP00000384330.2	P13535
MYHAS	ENST00000399342.6	TSL:3	n.206+2878G>A		intron	N/A
MYHAS	ENST00000581304.2	TSL:3	n.143+2917G>A		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.0535

AC:

8130

AN:

152048

Hom.:

245

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0418

Gnomad AMI

AF:

0.0581

Gnomad AMR

AF:

0.0475

Gnomad ASJ

AF:

0.0792

Gnomad EAS

AF:

0.0410

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0529

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.0564

Gnomad OTH

AF:

0.0679

GnomAD2 exomes

AF:

0.0589

AC:

14805

AN:

251236

AF XY:

0.0624

show subpopulations

Gnomad AFR exome

AF:

0.0403

Gnomad AMR exome

AF:

0.0439

Gnomad ASJ exome

AF:

0.0800

Gnomad EAS exome

AF:

0.0357

Gnomad FIN exome

AF:

0.0546

Gnomad NFE exome

AF:

0.0549

Gnomad OTH exome

AF:

0.0588

GnomAD4 exome

AF:

0.0581

AC:

84872

AN:

1461488

Hom.:

2840

Cov.:

AF XY:

0.0596

AC XY:

43357

AN XY:

727098

show subpopulations

African (AFR)

AF:

0.0432

AC:

1446

AN:

33472

American (AMR)

AF:

0.0443

AC:

1981

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0811

AC:

2118

AN:

26130

East Asian (EAS)

AF:

0.0356

AC:

1415

AN:

39694

South Asian (SAS)

AF:

0.109

AC:

9438

AN:

86242

European-Finnish (FIN)

AF:

0.0538

AC:

2872

AN:

53416

Middle Eastern (MID)

AF:

0.0560

AC:

323

AN:

5768

European-Non Finnish (NFE)

AF:

0.0554

AC:

61598

AN:

1111662

Other (OTH)

AF:

0.0610

AC:

3681

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

4260

8520

12781

17041

21301

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2406

4812

7218

9624

12030

<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:

0.0536

AC:

8152

AN:

152166

Hom.:

248

Cov.:

AF XY:

0.0549

AC XY:

4082

AN XY:

74370

show subpopulations

African (AFR)

AF:

0.0421

AC:

1748

AN:

41508

American (AMR)

AF:

0.0475

AC:

726

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0792

AC:

275

AN:

3472

East Asian (EAS)

AF:

0.0407

AC:

211

AN:

5184

South Asian (SAS)

AF:

0.121

AC:

583

AN:

4826

European-Finnish (FIN)

AF:

0.0529

AC:

559

AN:

10558

Middle Eastern (MID)

AF:

0.0685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0564

AC:

3833

AN:

68010

Other (OTH)

AF:

0.0682

AC:

144

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

399

798

1198

1597

1996

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

192

288

384

480

<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:

0.0541

Hom.:

804

Bravo

AF:

0.0508

TwinsUK

AF:

0.0520

AC:

193

ALSPAC

AF:

0.0522

AC:

201

ESP6500AA

AF:

0.0452

AC:

199

ESP6500EA

AF:

0.0610

AC:

525

ExAC

AF:

0.0591

AC:

7178

Asia WGS

AF:

0.0900

AC:

313

AN:

3478

EpiCase

AF:

0.0575

EpiControl

AF:

0.0577

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

Hecht syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.36

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.32

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.25

MetaRNN

Benign

0.0020

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.96

PhyloP100

1.5

PrimateAI

Benign

0.43

PROVEAN

Benign

-1.6

REVEL

Benign

0.17

Sift

Benign

0.048

Sift4G

Benign

0.44

Polyphen

0.0

Vest4

0.097

MPC

0.20

ClinPred

0.029

GERP RS

5.2

Varity_R

0.088

gMVP

0.15

Mutation Taster

=93/7

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over