17-10401183-C-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.3117G>A(p.Gly1039Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0586 in 1,613,636 control chromosomes in the GnomAD database, including 3,202 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.048 ( 225 hom., cov: 32)

Exomes 𝑓: 0.060 ( 2977 hom. )

Consequence

MYH8
NM_002472.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -3.92

Publications

8 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=-0.65).

BP6

Variant 17-10401183-C-T is Benign according to our data. Variant chr17-10401183-C-T is described in ClinVar as Benign. ClinVar VariationId is 129673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-3.92 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.115 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH8	NM_002472.3 link	c.3117G>A	p.Gly1039Gly	synonymous_variant	Exon 25 of 40	ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1 link	n.77-4965C>T		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2 link	c.3117G>A	p.Gly1039Gly	synonymous_variant	Exon 25 of 40	5	NM_002472.3	ENSP00000384330.2

Frequencies

GnomAD3 genomes

AF:

0.0481

AC:

7321

AN:

152076

Hom.:

224

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0204

Gnomad AMI

AF:

0.0747

Gnomad AMR

AF:

0.0421

Gnomad ASJ

AF:

0.0832

Gnomad EAS

AF:

0.0271

Gnomad SAS

AF:

0.123

Gnomad FIN

AF:

0.0571

Gnomad MID

AF:

0.0696

Gnomad NFE

AF:

0.0586

Gnomad OTH

AF:

0.0637

GnomAD2 exomes

AF:

0.0578

AC:

14516

AN:

251290

AF XY:

0.0622

show subpopulations

Gnomad AFR exome

AF:

0.0183

Gnomad AMR exome

AF:

0.0348

Gnomad ASJ exome

AF:

0.0839

Gnomad EAS exome

AF:

0.0220

Gnomad FIN exome

AF:

0.0595

Gnomad NFE exome

AF:

0.0586

Gnomad OTH exome

AF:

0.0583

GnomAD4 exome

AF:

0.0597

AC:

87180

AN:

1461442

Hom.:

2977

Cov.:

AF XY:

0.0613

AC XY:

44587

AN XY:

726996

show subpopulations

African (AFR)

AF:

0.0190

AC:

637

AN:

33450

American (AMR)

AF:

0.0359

AC:

1606

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.0857

AC:

2240

AN:

26128

East Asian (EAS)

AF:

0.0285

AC:

1133

AN:

39698

South Asian (SAS)

AF:

0.112

AC:

9667

AN:

86044

European-Finnish (FIN)

AF:

0.0600

AC:

3205

AN:

53416

Middle Eastern (MID)

AF:

0.0562

AC:

324

AN:

5766

European-Non Finnish (NFE)

AF:

0.0582

AC:

64691

AN:

1111854

Other (OTH)

AF:

0.0609

AC:

3677

AN:

60384

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

Heterozygous variant carriers

4700

9400

14100

18800

23500

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2486

4972

7458

9944

12430

<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:

0.0481

AC:

7324

AN:

152194

Hom.:

225

Cov.:

AF XY:

0.0495

AC XY:

3684

AN XY:

74388

show subpopulations

African (AFR)

AF:

0.0203

AC:

844

AN:

41534

American (AMR)

AF:

0.0420

AC:

642

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0832

AC:

289

AN:

3472

East Asian (EAS)

AF:

0.0272

AC:

141

AN:

5182

South Asian (SAS)

AF:

0.124

AC:

596

AN:

4820

European-Finnish (FIN)

AF:

0.0571

AC:

604

AN:

10578

Middle Eastern (MID)

AF:

0.0714

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0586

AC:

3987

AN:

68010

Other (OTH)

AF:

0.0626

AC:

132

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

371

742

1114

1485

1856

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<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:

0.0488

Hom.:

185

Bravo

AF:

0.0445

Asia WGS

AF:

0.0700

AC:

241

AN:

3478

EpiCase

AF:

0.0595

EpiControl

AF:

0.0612

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Oct 30, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Hecht syndrome

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

3.3

(source)

DANN

Benign

0.74

PhyloP100

-3.9

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