Variant rs73976871 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.5160+30G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0378 in 1,614,006 control chromosomes in the GnomAD database, including 1,398 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.039 ( 140 hom., cov: 32)

Exomes 𝑓: 0.038 ( 1258 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.723

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:

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=-0.8).

BP6

Variant 17-10631783-C-A is Benign according to our data. Variant chr17-10631783-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 258694.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0637 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.5160+30G>T		intron_variant		ENST00000583535.6	NP_002461.2
LOC124903927	XR_007065620.1 linkuse as main transcript	n.221+19C>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.5160+30G>T		intron_variant		5	NM_002470.4	ENSP00000464317	P1

Frequencies

GnomAD3 genomes

AF:

0.0391

AC:

5941

AN:

151998

Hom.:

140

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0612

Gnomad AMI

AF:

0.0482

Gnomad AMR

AF:

0.0192

Gnomad ASJ

AF:

0.0277

Gnomad EAS

AF:

0.00831

Gnomad SAS

AF:

0.0696

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0349

Gnomad OTH

AF:

0.0327

GnomAD3 exomes

AF:

0.0331

AC:

8334

AN:

251432

Hom.:

217

AF XY:

0.0343

AC XY:

4665

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.0578

Gnomad AMR exome

AF:

0.0125

Gnomad ASJ exome

AF:

0.0233

Gnomad EAS exome

AF:

0.0103

Gnomad SAS exome

AF:

0.0664

Gnomad FIN exome

AF:

0.0162

Gnomad NFE exome

AF:

0.0349

Gnomad OTH exome

AF:

0.0305

GnomAD4 exome

AF:

0.0377

AC:

55123

AN:

1461890

Hom.:

1258

Cov.:

AF XY:

0.0380

AC XY:

27599

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0651

Gnomad4 AMR exome

AF:

0.0124

Gnomad4 ASJ exome

AF:

0.0235

Gnomad4 EAS exome

AF:

0.00945

Gnomad4 SAS exome

AF:

0.0653

Gnomad4 FIN exome

AF:

0.0172

Gnomad4 NFE exome

AF:

0.0381

Gnomad4 OTH exome

AF:

0.0385

GnomAD4 genome

AF:

0.0391

AC:

5945

AN:

152116

Hom.:

140

Cov.:

AF XY:

0.0383

AC XY:

2848

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0612

Gnomad4 AMR

AF:

0.0192

Gnomad4 ASJ

AF:

0.0277

Gnomad4 EAS

AF:

0.00833

Gnomad4 SAS

AF:

0.0699

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.0349

Gnomad4 OTH

AF:

0.0328

Alfa

AF:

0.0341

Hom.:

Bravo

AF:

0.0391

Asia WGS

AF:

0.0350

AC:

120

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 26, 2019	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.099

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