rs8069834

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002472.3(MYH8):c.5074T>C(p.Trp1692Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.562 in 1,613,742 control chromosomes in the GnomAD database, including 263,923 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 27438 hom., cov: 30)

Exomes 𝑓: 0.56 ( 236485 hom. )

Consequence

MYH8
NM_002472.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.738

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:

ENSG00000272736 (HGNC:):

ENSG00000272736 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 made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.2877016E-6).

BP6

Variant 17-10394341-A-G is Benign according to our data. Variant chr17-10394341-A-G is described in ClinVar as [Benign]. Clinvar id is 129678.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10394341-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.717 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH8	NM_002472.3 link	c.5074T>C	p.Trp1692Arg	missense_variant	Exon 35 of 40	ENST00000403437.2	NP_002463.2	P13535
MYHAS	NR_125367.1 link	n.76+11134A>G		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH8	ENST00000403437.2 link	c.5074T>C	p.Trp1692Arg	missense_variant	Exon 35 of 40	5	NM_002472.3	ENSP00000384330.2	P13535
ENSG00000272736	ENST00000399342.6 link	n.76+11134A>G		intron_variant	Intron 1 of 3	3
ENSG00000272736	ENST00000581304.1 link	n.52+11134A>G		intron_variant	Intron 1 of 3	3
MYHAS	ENST00000587182.2 link	n.64+11134A>G		intron_variant	Intron 1 of 10	5

Frequencies

GnomAD3 genomes

AF:

0.588

AC:

89225

AN:

151748

Hom.:

27416

Cov.:

show subpopulations

Gnomad AFR

AF:

0.724

Gnomad AMI

AF:

0.518

Gnomad AMR

AF:

0.512

Gnomad ASJ

AF:

0.543

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.344

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.585

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.610

GnomAD3 exomes

AF:

0.500

AC:

125849

AN:

251466

Hom.:

34468

AF XY:

0.499

AC XY:

67807

AN XY:

135910

show subpopulations

Gnomad AFR exome

AF:

0.732

Gnomad AMR exome

AF:

0.395

Gnomad ASJ exome

AF:

0.542

Gnomad EAS exome

AF:

0.113

Gnomad SAS exome

AF:

0.353

Gnomad FIN exome

AF:

0.523

Gnomad NFE exome

AF:

0.591

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.559

AC:

817696

AN:

1461876

Hom.:

236485

Cov.:

AF XY:

0.554

AC XY:

403049

AN XY:

727234

show subpopulations

Gnomad4 AFR exome

AF:

0.734

Gnomad4 AMR exome

AF:

0.413

Gnomad4 ASJ exome

AF:

0.540

Gnomad4 EAS exome

AF:

0.151

Gnomad4 SAS exome

AF:

0.359

Gnomad4 FIN exome

AF:

0.534

Gnomad4 NFE exome

AF:

0.592

Gnomad4 OTH exome

AF:

0.548

GnomAD4 genome

AF:

0.588

AC:

89296

AN:

151866

Hom.:

27438

Cov.:

AF XY:

0.575

AC XY:

42635

AN XY:

74192

show subpopulations

Gnomad4 AFR

AF:

0.723

Gnomad4 AMR

AF:

0.512

Gnomad4 ASJ

AF:

0.543

Gnomad4 EAS

AF:

0.134

Gnomad4 SAS

AF:

0.344

Gnomad4 FIN

AF:

0.519

Gnomad4 NFE

AF:

0.588

Gnomad4 OTH

AF:

0.608

Alfa

AF:

0.576

Hom.:

9935

Bravo

AF:

0.597

TwinsUK

AF:

0.598

AC:

2219

ALSPAC

AF:

0.592

AC:

2282

ESP6500AA

AF:

0.721

AC:

3176

ESP6500EA

AF:

0.583

AC:

5013

ExAC

AF:

0.509

AC:

61857

Asia WGS

AF:

0.281

AC:

983

AN:

3478

EpiCase

AF:

0.600

EpiControl

AF:

0.597

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

- -

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

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Hecht syndrome

Benign:2

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. -

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 05, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.044

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

7.4

DANN

Benign

0.77

DEOGEN2

Benign

0.14

Eigen

Benign

-1.2

Eigen_PC

Benign

-0.88

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.18

MetaRNN

Benign

0.0000013

MetaSVM

Benign

-0.89

MutationAssessor

Benign

-4.2

PrimateAI

Benign

0.36

PROVEAN

Benign

5.3

REVEL

Benign

0.18

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.031

MutPred

0.15

Gain of disorder (P = 0.0122);

MPC

0.35

ClinPred

0.0038

GERP RS

1.8

Varity_R

0.052

gMVP

0.33

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over