17-10629567-G-A

Variant summary

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

The NM_002470.4(MYH3):c.5796+30C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 1,611,162 control chromosomes in the GnomAD database, including 392,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 29291 hom., cov: 32)

Exomes 𝑓: 0.70 ( 362800 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -0.683

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=-0.8).

BP6

Variant 17-10629567-G-A is Benign according to our data. Variant chr17-10629567-G-A is described in ClinVar as [Benign]. Clinvar id is 258701.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.733 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MYH3	NM_002470.4 linkuse as main transcript	c.5796+30C>T	intron_variant	ENST00000583535.6
MYH3	XM_011523870.4 linkuse as main transcript	c.5796+30C>T	intron_variant
MYH3	XM_011523871.3 linkuse as main transcript	c.5796+30C>T	intron_variant
MYH3	XM_047436127.1 linkuse as main transcript	c.5796+30C>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
MYH3	ENST00000583535.6 linkuse as main transcript	c.5796+30C>T	intron_variant	5	NM_002470.4	P1
MYH3	ENST00000577963.1 linkuse as main transcript	n.338+30C>T	intron_variant, non_coding_transcript_variant	2
MYH3	ENST00000579928.2 linkuse as main transcript	n.326+30C>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.592

AC:

89693

AN:

151584

Hom.:

29291

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.744

Gnomad AMR

AF:

0.620

Gnomad ASJ

AF:

0.711

Gnomad EAS

AF:

0.521

Gnomad SAS

AF:

0.537

Gnomad FIN

AF:

0.740

Gnomad MID

AF:

0.547

Gnomad NFE

AF:

0.739

Gnomad OTH

AF:

0.604

GnomAD3 exomes

AF:

0.648

AC:

162246

AN:

250480

Hom.:

54575

AF XY:

0.655

AC XY:

88742

AN XY:

135540

show subpopulations

Gnomad AFR exome

AF:

0.299

Gnomad AMR exome

AF:

0.595

Gnomad ASJ exome

AF:

0.715

Gnomad EAS exome

AF:

0.519

Gnomad SAS exome

AF:

0.552

Gnomad FIN exome

AF:

0.747

Gnomad NFE exome

AF:

0.733

Gnomad OTH exome

AF:

0.678

GnomAD4 exome

AF:

0.699

AC:

1020484

AN:

1459464

Hom.:

362800

Cov.:

AF XY:

0.697

AC XY:

506337

AN XY:

726034

show subpopulations

Gnomad4 AFR exome

AF:

0.278

Gnomad4 AMR exome

AF:

0.601

Gnomad4 ASJ exome

AF:

0.713

Gnomad4 EAS exome

AF:

0.526

Gnomad4 SAS exome

AF:

0.552

Gnomad4 FIN exome

AF:

0.751

Gnomad4 NFE exome

AF:

0.733

Gnomad4 OTH exome

AF:

0.666

GnomAD4 genome

AF:

0.591

AC:

89716

AN:

151698

Hom.:

29291

Cov.:

AF XY:

0.589

AC XY:

43715

AN XY:

74162

show subpopulations

Gnomad4 AFR

AF:

0.300

Gnomad4 AMR

AF:

0.620

Gnomad4 ASJ

AF:

0.711

Gnomad4 EAS

AF:

0.522

Gnomad4 SAS

AF:

0.536

Gnomad4 FIN

AF:

0.740

Gnomad4 NFE

AF:

0.739

Gnomad4 OTH

AF:

0.606

Alfa

AF:

0.630

Hom.:

4095

Bravo

AF:

0.568

Asia WGS

AF:

0.517

AC:

1790

AN:

3456

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

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

-0.80

Cadd

Benign

2.5

Dann

Benign

0.88

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