17-10639569-T-C

Variant names:

Variant summary

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

The NM_002470.4(MYH3):c.2916A>G(p.Thr972Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,613,792 control chromosomes in the GnomAD database, including 379,770 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27813 hom., cov: 32)

Exomes 𝑓: 0.69 ( 351957 hom. )

Consequence

MYH3
NM_002470.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:14

Conservation

PhyloP100: -3.87

Variant links:

Genes affected

MYH3 (HGNC:7573): (myosin heavy chain 3) Myosin is a major contractile protein which converts chemical energy into mechanical energy through the hydrolysis of ATP. Myosin is a hexameric protein composed of a pair of myosin heavy chains (MYH) and two pairs of nonidentical light chains. This gene is a member of the MYH family and encodes a protein with an IQ domain and a myosin head-like domain. Mutations in this gene have been associated with two congenital contracture (arthrogryposis) syndromes, Freeman-Sheldon syndrome and Sheldon-Hall syndrome. [provided by RefSeq, Jul 2008]

MYH3 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=-0.61).

BP6

Variant 17-10639569-T-C is Benign according to our data. Variant chr17-10639569-T-C is described in ClinVar as [Benign]. Clinvar id is 129652.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10639569-T-C is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-3.87 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.728 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH3	NM_002470.4 link	c.2916A>G	p.Thr972Thr	synonymous_variant	Exon 23 of 41	ENST00000583535.6	NP_002461.2	P11055Q5GJ67
MYH3	XM_011523870.4 link	c.2916A>G	p.Thr972Thr	synonymous_variant	Exon 23 of 41		XP_011522172.1	P11055
MYH3	XM_011523871.3 link	c.2916A>G	p.Thr972Thr	synonymous_variant	Exon 23 of 41		XP_011522173.1	P11055
MYH3	XM_047436127.1 link	c.2916A>G	p.Thr972Thr	synonymous_variant	Exon 25 of 43		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6 link	c.2916A>G	p.Thr972Thr	synonymous_variant	Exon 23 of 41	5	NM_002470.4	ENSP00000464317.1		P11055

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

87065

AN:

151930

Hom.:

27807

Cov.:

show subpopulations

Gnomad AFR

AF:

0.295

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.523

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.734

Gnomad OTH

AF:

0.591

GnomAD3 exomes

AF:

0.610

AC:

153454

AN:

251488

Hom.:

49780

AF XY:

0.622

AC XY:

84581

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.708

Gnomad EAS exome

AF:

0.362

Gnomad SAS exome

AF:

0.538

Gnomad FIN exome

AF:

0.714

Gnomad NFE exome

AF:

0.728

Gnomad OTH exome

AF:

0.653

GnomAD4 exome

AF:

0.686

AC:

1002176

AN:

1461744

Hom.:

351957

Cov.:

AF XY:

0.684

AC XY:

497604

AN XY:

727168

show subpopulations

Gnomad4 AFR exome

AF:

0.277

Gnomad4 AMR exome

AF:

0.480

Gnomad4 ASJ exome

AF:

0.705

Gnomad4 EAS exome

AF:

0.368

Gnomad4 SAS exome

AF:

0.539

Gnomad4 FIN exome

AF:

0.720

Gnomad4 NFE exome

AF:

0.729

Gnomad4 OTH exome

AF:

0.653

GnomAD4 genome

AF:

0.573

AC:

87097

AN:

152048

Hom.:

27813

Cov.:

AF XY:

0.568

AC XY:

42192

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.561

Gnomad4 ASJ

AF:

0.703

Gnomad4 EAS

AF:

0.373

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.706

Gnomad4 NFE

AF:

0.734

Gnomad4 OTH

AF:

0.595

Alfa

AF:

0.666

Hom.:

24333

Bravo

AF:

0.547

Asia WGS

AF:

0.464

AC:

1620

AN:

3478

EpiCase

AF:

0.730

EpiControl

AF:

0.724

ClinVar

Significance: Benign

Submissions summary: Benign:14

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

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

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided

Benign:3

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Freeman-Sheldon syndrome

Benign:2

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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. -

Contractures, pterygia, and variable skeletal fusions syndrome 1B

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Arthrogryposis, distal, type 2B3

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Distal arthrogryposis type 2B1

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.64

DANN

Benign

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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