rs12936716

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id is 129672.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10406929-G-A is described in Lovd as [Benign].

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	UniProt
MYH8	ENST00000403437.2 link	c.2016C>T	p.Phe672Phe	synonymous_variant	Exon 18 of 40	5	NM_002472.3	ENSP00000384330.2	P13535
ENSG00000272736	ENST00000399342.6 link	n.206+652G>A		intron_variant	Intron 2 of 3	3
ENSG00000272736	ENST00000581304.1 link	n.143+691G>A		intron_variant	Intron 2 of 3	3
MYHAS	ENST00000587182.2 link	n.155+691G>A		intron_variant	Intron 2 of 10	5

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

GnomAD3 exomes

AF:

0.0564

AC:

14168

AN:

251414

Hom.:

523

AF XY:

0.0602

AC XY:

8186

AN XY:

135874

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 SAS exome

AF:

0.109

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

Gnomad4 AFR exome

AF:

0.0418

Gnomad4 AMR exome

AF:

0.0363

Gnomad4 ASJ exome

AF:

0.0811

Gnomad4 EAS exome

AF:

0.0288

Gnomad4 SAS exome

AF:

0.108

Gnomad4 FIN exome

AF:

0.0538

Gnomad4 NFE exome

AF:

0.0553

Gnomad4 OTH exome

AF:

0.0593

GnomAD4 genome

AF:

0.0521

AC:

7933

AN:

152206

Hom.:

237

Cov.:

AF XY:

0.0534

AC XY:

3972

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.0434

Gnomad4 ASJ

AF:

0.0784

Gnomad4 EAS

AF:

0.0283

Gnomad4 SAS

AF:

0.118

Gnomad4 FIN

AF:

0.0528

Gnomad4 NFE

AF:

0.0562

Gnomad4 OTH

AF:

0.0643

Alfa

AF:

0.0564

Hom.:

251

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 28, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

DANN

Benign

0.81

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

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