NM_002472.3:c.3117G>A

Variant names:

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 129673.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10401183-C-T is described in Lovd as [Benign].

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	P13535
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	UniProt
MYH8	ENST00000403437.2 link	c.3117G>A	p.Gly1039Gly	synonymous_variant	Exon 25 of 40	5	NM_002472.3	ENSP00000384330.2	P13535
ENSG00000272736	ENST00000399342.6 link	n.77-4965C>T		intron_variant	Intron 1 of 3	3
ENSG00000272736	ENST00000581304.1 link	n.53-4965C>T		intron_variant	Intron 1 of 3	3
MYHAS	ENST00000587182.2 link	n.65-4965C>T		intron_variant	Intron 1 of 10	5

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

GnomAD3 exomes

AF:

0.0578

AC:

14516

AN:

251290

Hom.:

555

AF XY:

0.0622

AC XY:

8450

AN XY:

135854

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 SAS exome

AF:

0.113

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

Gnomad4 AFR exome

AF:

0.0190

Gnomad4 AMR exome

AF:

0.0359

Gnomad4 ASJ exome

AF:

0.0857

Gnomad4 EAS exome

AF:

0.0285

Gnomad4 SAS exome

AF:

0.112

Gnomad4 FIN exome

AF:

0.0600

Gnomad4 NFE exome

AF:

0.0582

Gnomad4 OTH exome

AF:

0.0609

GnomAD4 genome

AF:

0.0481

AC:

7324

AN:

152194

Hom.:

225

Cov.:

AF XY:

0.0495

AC XY:

3684

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0203

Gnomad4 AMR

AF:

0.0420

Gnomad4 ASJ

AF:

0.0832

Gnomad4 EAS

AF:

0.0272

Gnomad4 SAS

AF:

0.124

Gnomad4 FIN

AF:

0.0571

Gnomad4 NFE

AF:

0.0586

Gnomad4 OTH

AF:

0.0626

Alfa

AF:

0.0474

Hom.:

123

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 30, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

DANN

Benign

0.74

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