chr17-10400944-G-A

Position:

chr17-10400944-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.3270C>T(p.Ile1090=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.557 in 1,612,782 control chromosomes in the GnomAD database, including 259,373 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26507 hom., cov: 33)

Exomes 𝑓: 0.56 ( 232866 hom. )

Consequence

MYH8
NM_002472.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.295

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 17-10400944-G-A is Benign according to our data. Variant chr17-10400944-G-A is described in ClinVar as [Benign]. Clinvar id is 129674.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10400944-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.295 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 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.3270C>T	p.Ile1090=	synonymous_variant	26/40	ENST00000403437.2	NP_002463.2
MYHAS	NR_125367.1 linkuse as main transcript	n.77-5204G>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.3270C>T	p.Ile1090=	synonymous_variant	26/40	5	NM_002472.3	ENSP00000384330	P1
	ENST00000399342.6 linkuse as main transcript	n.77-5204G>A		intron_variant, non_coding_transcript_variant		3
	ENST00000581304.1 linkuse as main transcript	n.53-5204G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes

AF:

0.578

AC:

87907

AN:

151986

Hom.:

26487

Cov.:

show subpopulations

Gnomad AFR

AF:

0.699

Gnomad AMI

AF:

0.503

Gnomad AMR

AF:

0.506

Gnomad ASJ

AF:

0.537

Gnomad EAS

AF:

0.133

Gnomad SAS

AF:

0.332

Gnomad FIN

AF:

0.515

Gnomad MID

AF:

0.582

Gnomad NFE

AF:

0.585

Gnomad OTH

AF:

0.603

GnomAD3 exomes

AF:

0.494

AC:

123748

AN:

250446

Hom.:

33409

AF XY:

0.493

AC XY:

66736

AN XY:

135472

show subpopulations

Gnomad AFR exome

AF:

0.707

Gnomad AMR exome

AF:

0.392

Gnomad ASJ exome

AF:

0.538

Gnomad EAS exome

AF:

0.113

Gnomad SAS exome

AF:

0.342

Gnomad FIN exome

AF:

0.518

Gnomad NFE exome

AF:

0.587

Gnomad OTH exome

AF:

0.539

GnomAD4 exome

AF:

0.555

AC:

810901

AN:

1460680

Hom.:

232866

Cov.:

AF XY:

0.550

AC XY:

399595

AN XY:

726656

show subpopulations

Gnomad4 AFR exome

AF:

0.708

Gnomad4 AMR exome

AF:

0.410

Gnomad4 ASJ exome

AF:

0.536

Gnomad4 EAS exome

AF:

0.150

Gnomad4 SAS exome

AF:

0.348

Gnomad4 FIN exome

AF:

0.528

Gnomad4 NFE exome

AF:

0.589

Gnomad4 OTH exome

AF:

0.543

GnomAD4 genome

AF:

0.578

AC:

87977

AN:

152102

Hom.:

26507

Cov.:

AF XY:

0.565

AC XY:

41995

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.699

Gnomad4 AMR

AF:

0.506

Gnomad4 ASJ

AF:

0.537

Gnomad4 EAS

AF:

0.134

Gnomad4 SAS

AF:

0.332

Gnomad4 FIN

AF:

0.515

Gnomad4 NFE

AF:

0.585

Gnomad4 OTH

AF:

0.602

Alfa

AF:

0.580

Hom.:

49411

Bravo

AF:

0.587

Asia WGS

AF:

0.276

AC:

963

AN:

3478

EpiCase

AF:

0.597

EpiControl

AF:

0.592

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

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

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

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

5.3

DANN

Benign

0.73

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