rs2285467

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002470.4(MYH3):c.349-36A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 1,605,336 control chromosomes in the GnomAD database, including 14,728 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1312 hom., cov: 31)

Exomes 𝑓: 0.13 ( 13416 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.427

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 17-10651704-T-C is Benign according to our data. Variant chr17-10651704-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 258681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MYH3	NM_002470.4 linkuse as main transcript	c.349-36A>G	intron_variant	ENST00000583535.6
MYH3	XM_011523870.4 linkuse as main transcript	c.349-36A>G	intron_variant
MYH3	XM_011523871.3 linkuse as main transcript	c.349-36A>G	intron_variant
MYH3	XM_047436127.1 linkuse as main transcript	c.349-36A>G	intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH3	ENST00000583535.6 linkuse as main transcript	c.349-36A>G		intron_variant		5	NM_002470.4	P1
MYH3	ENST00000579489.2 linkuse as main transcript	n.265A>G		non_coding_transcript_exon_variant	1/4	5

Frequencies

GnomAD3 genomes

AF:

0.129

AC:

19448

AN:

151322

Hom.:

1311

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.144

Gnomad AMR

AF:

0.114

Gnomad ASJ

AF:

0.136

Gnomad EAS

AF:

0.0403

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.129

Gnomad MID

AF:

0.122

Gnomad NFE

AF:

0.141

Gnomad OTH

AF:

0.139

GnomAD3 exomes

AF:

0.121

AC:

30290

AN:

250760

Hom.:

1937

AF XY:

0.125

AC XY:

16978

AN XY:

135638

show subpopulations

Gnomad AFR exome

AF:

0.129

Gnomad AMR exome

AF:

0.0693

Gnomad ASJ exome

AF:

0.141

Gnomad EAS exome

AF:

0.0410

Gnomad SAS exome

AF:

0.132

Gnomad FIN exome

AF:

0.134

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.132

GnomAD4 exome

AF:

0.133

AC:

193256

AN:

1453916

Hom.:

13416

Cov.:

AF XY:

0.134

AC XY:

96943

AN XY:

723818

show subpopulations

Gnomad4 AFR exome

AF:

0.121

Gnomad4 AMR exome

AF:

0.0739

Gnomad4 ASJ exome

AF:

0.141

Gnomad4 EAS exome

AF:

0.0362

Gnomad4 SAS exome

AF:

0.133

Gnomad4 FIN exome

AF:

0.131

Gnomad4 NFE exome

AF:

0.139

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.128

AC:

19446

AN:

151420

Hom.:

1312

Cov.:

AF XY:

0.128

AC XY:

9439

AN XY:

73894

show subpopulations

Gnomad4 AFR

AF:

0.122

Gnomad4 AMR

AF:

0.114

Gnomad4 ASJ

AF:

0.136

Gnomad4 EAS

AF:

0.0408

Gnomad4 SAS

AF:

0.129

Gnomad4 FIN

AF:

0.129

Gnomad4 NFE

AF:

0.141

Gnomad4 OTH

AF:

0.137

Alfa

AF:

0.134

Hom.:

340

Bravo

AF:

0.125

Asia WGS

AF:

0.0980

AC:

340

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Freeman-Sheldon syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2018

- -

Contractures, pterygia, and variable skeletal fusions syndrome 1B

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Arthrogryposis, distal, type 2B3

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

Cadd

Benign

2.7

Dann

Benign

0.24

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