rs35962914

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_002472.3(MYH8):c.3686T>C(p.Met1229Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.01 in 1,613,930 control chromosomes in the GnomAD database, including 109 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0072 ( 12 hom., cov: 32)

Exomes 𝑓: 0.010 ( 97 hom. )

Consequence

MYH8
NM_002472.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 9.06

Publications

12 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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0093815625).

BP6

Variant 17-10400439-A-G is Benign according to our data. Variant chr17-10400439-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129675.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 1093 AD gene.

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.3686T>C	p.Met1229Thr	missense	Exon 27 of 40	NP_002463.2	P13535
	MYHAS	NR_125367.1		n.77-5709A>G		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYH8	ENST00000403437.2	TSL:5 MANE Select	c.3686T>C	p.Met1229Thr	missense	Exon 27 of 40	ENSP00000384330.2	P13535
MYHAS	ENST00000399342.6	TSL:3	n.77-5709A>G		intron	N/A
MYHAS	ENST00000581304.2	TSL:3	n.53-5709A>G		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.00718

AC:

1092

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.0978

Gnomad AMR

AF:

0.00615

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00415

Gnomad FIN

AF:

0.00547

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0106

Gnomad OTH

AF:

0.00670

GnomAD2 exomes

AF:

0.00657

AC:

1652

AN:

251446

AF XY:

0.00685

show subpopulations

Gnomad AFR exome

AF:

0.00172

Gnomad AMR exome

AF:

0.00332

Gnomad ASJ exome

AF:

0.00198

Gnomad EAS exome

AF:

0.000109

Gnomad FIN exome

AF:

0.00513

Gnomad NFE exome

AF:

0.0105

Gnomad OTH exome

AF:

0.00749

GnomAD4 exome

AF:

0.0103

AC:

15072

AN:

1461692

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

7314

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.00149

AC:

AN:

33472

American (AMR)

AF:

0.00389

AC:

174

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.00172

AC:

AN:

26132

East Asian (EAS)

AF:

0.0000504

AC:

AN:

39700

South Asian (SAS)

AF:

0.00496

AC:

428

AN:

86250

European-Finnish (FIN)

AF:

0.00532

AC:

284

AN:

53362

Middle Eastern (MID)

AF:

0.000867

AC:

AN:

5764

European-Non Finnish (NFE)

AF:

0.0121

AC:

13508

AN:

1111918

Other (OTH)

AF:

0.00954

AC:

576

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

914

1828

2742

3656

4570

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.00718

AC:

1093

AN:

152238

Hom.:

Cov.:

AF XY:

0.00647

AC XY:

482

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.00207

AC:

AN:

41538

American (AMR)

AF:

0.00615

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00144

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00436

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00547

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0106

AC:

724

AN:

68006

Other (OTH)

AF:

0.00663

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

100

151

201

251

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00945

Hom.:

Bravo

AF:

0.00716

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0109

AC:

ESP6500AA

AF:

0.00250

AC:

ESP6500EA

AF:

0.0120

AC:

103

ExAC

AF:

0.00666

AC:

808

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.0118

EpiControl

AF:

0.0109

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Hecht syndrome (1)

Hecht syndrome;C1837245:Carney complex - trismus - pseudocamptodactyly syndrome (1)

MYH8-related disorder (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.23

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.50

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.69

MetaRNN

Benign

0.0094

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.6

PhyloP100

9.1

PrimateAI

Uncertain

0.72

PROVEAN

Uncertain

-3.5

REVEL

Uncertain

0.37

Sift

Pathogenic

0.0

Sift4G

Benign

0.59

Polyphen

0.044

Vest4

0.54

MVP

0.81

MPC

0.39

ClinPred

0.16

GERP RS

4.3

Varity_R

0.78

gMVP

0.57

Mutation Taster

=93/7

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over