NM_002472.3:c.3270C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002472.3(MYH8):c.3270C>T(p.Ile1090Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,612,782 control chromosomes in the GnomAD database, including 259,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26507 hom., cov: 33)

Exomes 𝑓: 0.56 ( 232866 hom. )

Consequence

MYH8
NM_002472.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -0.295

Publications

16 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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 17-10400944-G-A is Benign according to our data. Variant chr17-10400944-G-A is described in ClinVar as Benign. ClinVar VariationId is 129674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.295 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH8	NM_002472.3 link	c.3270C>T	p.Ile1090Ile	synonymous_variant	Exon 26 of 40	ENST00000403437.2	NP_002463.2	P13535
MYHAS	NR_125367.1 link	n.77-5204G>A		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2 link	c.3270C>T	p.Ile1090Ile	synonymous_variant	Exon 26 of 40	5	NM_002472.3	ENSP00000384330.2		P13535

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87907

AN:

151986

Hom.:

26487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.585

Gnomad OTH

AF:

0.603

GnomAD2 exomes

AF:

0.494

AC:

123748

AN:

250446

AF XY:

0.493

show subpopulations

Gnomad AFR exome

AF:

0.707

Gnomad AMR exome

AF:

0.392

Gnomad ASJ exome

AF:

0.538

Gnomad EAS exome

AF:

0.113

Gnomad FIN exome

AF:

0.518

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.555

AC:

810901

AN:

1460680

Hom.:

232866

Cov.:

AF XY:

0.550

AC XY:

399595

AN XY:

726656

show subpopulations

African (AFR)

AF:

0.708

AC:

23706

AN:

33462

American (AMR)

AF:

0.410

AC:

18335

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.536

AC:

13997

AN:

26130

East Asian (EAS)

AF:

0.150

AC:

5969

AN:

39698

South Asian (SAS)

AF:

0.348

AC:

30015

AN:

86236

European-Finnish (FIN)

AF:

0.528

AC:

27933

AN:

52952

Middle Eastern (MID)

AF:

0.561

AC:

3234

AN:

5766

European-Non Finnish (NFE)

AF:

0.589

AC:

654955

AN:

1111378

Other (OTH)

AF:

0.543

AC:

32757

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

19934

39867

59801

79734

99668

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17676

35352

53028

70704

88380

<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:

0.578

AC:

87977

AN:

152102

Hom.:

26507

Cov.:

AF XY:

0.565

AC XY:

41995

AN XY:

74336

show subpopulations

African (AFR)

AF:

0.699

AC:

29011

AN:

41532

American (AMR)

AF:

0.506

AC:

7734

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.537

AC:

1864

AN:

3468

East Asian (EAS)

AF:

0.134

AC:

690

AN:

5160

South Asian (SAS)

AF:

0.332

AC:

1602

AN:

4822

European-Finnish (FIN)

AF:

0.515

AC:

5441

AN:

10568

Middle Eastern (MID)

AF:

0.575

AC:

168

AN:

292

European-Non Finnish (NFE)

AF:

0.585

AC:

39738

AN:

67952

Other (OTH)

AF:

0.602

AC:

1270

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1837

3674

5510

7347

9184

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:

0.584

Hom.:

74283

Bravo

AF:

0.587

Asia WGS

AF:

0.276

AC:

963

AN:

3478

EpiCase

AF:

0.597

EpiControl

AF:

0.592

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Hecht syndrome

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 13, 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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.3

(source)

DANN

Benign

0.73

PhyloP100

-0.29

Mutation Taster

=99/1

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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