rs12936716

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002472.3(MYH8):c.2016C>T(p.Phe672Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0568 in 1,613,586 control chromosomes in the GnomAD database, including 3,012 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.052 ( 237 hom., cov: 32)

Exomes 𝑓: 0.057 ( 2775 hom. )

Consequence

MYH8
NM_002472.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.183

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.43).

BP6

Variant 17-10406929-G-A is Benign according to our data. Variant chr17-10406929-G-A is described in ClinVar as Benign. ClinVar VariationId is 129672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.183 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH8	NM_002472.3 link	c.2016C>T	p.Phe672Phe	synonymous_variant	Exon 18 of 40	ENST00000403437.2	NP_002463.2	P13535
MYHAS	NR_125367.1 link	n.167+691G>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH8	ENST00000403437.2 link	c.2016C>T	p.Phe672Phe	synonymous_variant	Exon 18 of 40	5	NM_002472.3	ENSP00000384330.2		P13535

Frequencies

GnomAD3 genomes

AF:

0.0521

AC:

7919

AN:

152090

Hom.:

235

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0406

Gnomad AMI

AF:

0.0582

Gnomad AMR

AF:

0.0434

Gnomad ASJ

AF:

0.0784

Gnomad EAS

AF:

0.0283

Gnomad SAS

AF:

0.117

Gnomad FIN

AF:

0.0528

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0562

Gnomad OTH

AF:

0.0654

GnomAD2 exomes

AF:

0.0564

AC:

14168

AN:

251414

AF XY:

0.0602

show subpopulations

Gnomad AFR exome

AF:

0.0393

Gnomad AMR exome

AF:

0.0352

Gnomad ASJ exome

AF:

0.0800

Gnomad EAS exome

AF:

0.0229

Gnomad FIN exome

AF:

0.0546

Gnomad NFE exome

AF:

0.0547

Gnomad OTH exome

AF:

0.0560

GnomAD4 exome

AF:

0.0573

AC:

83776

AN:

1461380

Hom.:

2775

Cov.:

AF XY:

0.0589

AC XY:

42841

AN XY:

727022

show subpopulations

African (AFR)

AF:

0.0418

AC:

1399

AN:

33474

American (AMR)

AF:

0.0363

AC:

1622

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0811

AC:

2118

AN:

26130

East Asian (EAS)

AF:

0.0288

AC:

1142

AN:

39694

South Asian (SAS)

AF:

0.108

AC:

9289

AN:

86228

European-Finnish (FIN)

AF:

0.0538

AC:

2873

AN:

53416

Middle Eastern (MID)

AF:

0.0560

AC:

323

AN:

5768

European-Non Finnish (NFE)

AF:

0.0553

AC:

61428

AN:

1111564

Other (OTH)

AF:

0.0593

AC:

3582

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

4060

8121

12181

16242

20302

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2384

4768

7152

9536

11920

<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:

0.0521

AC:

7933

AN:

152206

Hom.:

237

Cov.:

AF XY:

0.0534

AC XY:

3972

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.0408

AC:

1695

AN:

41542

American (AMR)

AF:

0.0434

AC:

663

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.0784

AC:

272

AN:

3468

East Asian (EAS)

AF:

0.0283

AC:

147

AN:

5186

South Asian (SAS)

AF:

0.118

AC:

568

AN:

4810

European-Finnish (FIN)

AF:

0.0528

AC:

559

AN:

10596

Middle Eastern (MID)

AF:

0.0719

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0562

AC:

3819

AN:

67998

Other (OTH)

AF:

0.0643

AC:

136

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

367

734

1100

1467

1834

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:

0.0559

Hom.:

298

Bravo

AF:

0.0492

Asia WGS

AF:

0.0710

AC:

245

AN:

3478

EpiCase

AF:

0.0574

EpiControl

AF:

0.0575

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 28, 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 12, 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

-0.43

CADD

Benign

0.79

(source)

DANN

Benign

0.81

PhyloP100

0.18

Mutation Taster

=70/30

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