Variant rs4792008 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_002470.4(MYH3):c.4956+32C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,604,222 control chromosomes in the GnomAD database, including 377,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 27810 hom., cov: 33)

Exomes 𝑓: 0.69 ( 349679 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 0.0540

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:

LOC124903927 (HGNC:):

LOC124903927 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 17-10632444-G-A is Benign according to our data. Variant chr17-10632444-G-A is described in ClinVar as [Benign]. Clinvar id is 258690.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH3	NM_002470.4 linkuse as main transcript	c.4956+32C>T		intron_variant		ENST00000583535.6	NP_002461.2
LOC124903927	XR_007065620.1 linkuse as main transcript	n.221+680G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH3	ENST00000583535.6 linkuse as main transcript	c.4956+32C>T		intron_variant		5	NM_002470.4	ENSP00000464317	P1

Frequencies

GnomAD3 genomes

AF:

0.573

AC:

87100

AN:

152014

Hom.:

27808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.296

Gnomad AMI

AF:

0.743

Gnomad AMR

AF:

0.561

Gnomad ASJ

AF:

0.703

Gnomad EAS

AF:

0.369

Gnomad SAS

AF:

0.524

Gnomad FIN

AF:

0.706

Gnomad MID

AF:

0.548

Gnomad NFE

AF:

0.733

Gnomad OTH

AF:

0.589

GnomAD3 exomes

AF:

0.607

AC:

148956

AN:

245230

Hom.:

48151

AF XY:

0.620

AC XY:

82597

AN XY:

133124

show subpopulations

Gnomad AFR exome

AF:

0.294

Gnomad AMR exome

AF:

0.467

Gnomad ASJ exome

AF:

0.707

Gnomad EAS exome

AF:

0.362

Gnomad SAS exome

AF:

0.540

Gnomad FIN exome

AF:

0.714

Gnomad NFE exome

AF:

0.727

Gnomad OTH exome

AF:

0.652

GnomAD4 exome

AF:

0.686

AC:

995503

AN:

1452090

Hom.:

349679

Cov.:

AF XY:

0.684

AC XY:

494676

AN XY:

722910

show subpopulations

Gnomad4 AFR exome

AF:

0.277

Gnomad4 AMR exome

AF:

0.479

Gnomad4 ASJ exome

AF:

0.704

Gnomad4 EAS exome

AF:

0.367

Gnomad4 SAS exome

AF:

0.540

Gnomad4 FIN exome

AF:

0.719

Gnomad4 NFE exome

AF:

0.729

Gnomad4 OTH exome

AF:

0.652

GnomAD4 genome

AF:

0.573

AC:

87125

AN:

152132

Hom.:

27810

Cov.:

AF XY:

0.568

AC XY:

42234

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.295

Gnomad4 AMR

AF:

0.561

Gnomad4 ASJ

AF:

0.703

Gnomad4 EAS

AF:

0.371

Gnomad4 SAS

AF:

0.523

Gnomad4 FIN

AF:

0.706

Gnomad4 NFE

AF:

0.733

Gnomad4 OTH

AF:

0.589

Alfa

AF:

0.655

Hom.:

12553

Bravo

AF:

0.547

Asia WGS

AF:

0.448

AC:

1564

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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	-	- -

not specified

Benign:1

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

- -

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

-0.82

CADD

Benign

1.8

DANN

Benign

0.73

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