17-10393169-G-A

Position:

chr17-10393169-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002472.3(MYH8):c.5208C>T(p.Asp1736=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,613,884 control chromosomes in the GnomAD database, including 41,996 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2878 hom., cov: 32)

Exomes 𝑓: 0.22 ( 39118 hom. )

Consequence

MYH8
NM_002472.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0750

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:

(HGNC:):

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=-0.51).

BP6

Variant 17-10393169-G-A is Benign according to our data. Variant chr17-10393169-G-A is described in ClinVar as [Benign]. Clinvar id is 129679.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10393169-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.075 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.245 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH8	NM_002472.3 linkuse as main transcript	c.5208C>T	p.Asp1736=	synonymous_variant	36/40	ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1 linkuse as main transcript	n.76+9962G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
MYH8	ENST00000403437.2 linkuse as main transcript	c.5208C>T	p.Asp1736=	synonymous_variant	36/40	5	NM_002472.3	ENSP00000384330	P1
	ENST00000399342.6 linkuse as main transcript	n.76+9962G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1 linkuse as main transcript	n.52+9962G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.168

AC:

25559

AN:

152002

Hom.:

2879

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0509

Gnomad AMI

AF:

0.283

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.00154

Gnomad SAS

AF:

0.0710

Gnomad FIN

AF:

0.204

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.249

Gnomad OTH

AF:

0.197

GnomAD3 exomes

AF:

0.175

AC:

43906

AN:

251370

Hom.:

4929

AF XY:

0.178

AC XY:

24154

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0445

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.262

Gnomad EAS exome

AF:

0.000544

Gnomad SAS exome

AF:

0.0759

Gnomad FIN exome

AF:

0.203

Gnomad NFE exome

AF:

0.251

Gnomad OTH exome

AF:

0.217

GnomAD4 exome

AF:

0.221

AC:

322319

AN:

1461764

Hom.:

39118

Cov.:

AF XY:

0.217

AC XY:

158148

AN XY:

727180

show subpopulations

Gnomad4 AFR exome

AF:

0.0434

Gnomad4 AMR exome

AF:

0.123

Gnomad4 ASJ exome

AF:

0.262

Gnomad4 EAS exome

AF:

0.000378

Gnomad4 SAS exome

AF:

0.0800

Gnomad4 FIN exome

AF:

0.209

Gnomad4 NFE exome

AF:

0.249

Gnomad4 OTH exome

AF:

0.204

GnomAD4 genome

AF:

0.168

AC:

25557

AN:

152120

Hom.:

2878

Cov.:

AF XY:

0.164

AC XY:

12158

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.0508

Gnomad4 AMR

AF:

0.157

Gnomad4 ASJ

AF:

0.261

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.0710

Gnomad4 FIN

AF:

0.204

Gnomad4 NFE

AF:

0.249

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.222

Hom.:

2106

Bravo

AF:

0.163

Asia WGS

AF:

0.0420

AC:

147

AN:

3478

EpiCase

AF:

0.259

EpiControl

AF:

0.256

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genetic Services Laboratory, University of Chicago	Aug 15, 2013	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

Hecht syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

4.7

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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