dbSNP rs147333978: MYH3:c.5796+31_5796+32delCC (chr17-10629564-TGG-T) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BS2_Supporting

The NM_002470.4(MYH3):c.5796+31_5796+32delCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000804 in 1,580,522 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00017 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000071 ( 2 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BS2

High AC in GnomAd4 at 26 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH3	NM_002470.4 link	c.5796+31_5796+32delCC	intron_variant	Intron 40 of 40	ENST00000583535.6	NP_002461.2	P11055Q5GJ67
MYH3	XM_011523870.4 link	c.5796+31_5796+32delCC	intron_variant	Intron 40 of 40		XP_011522172.1	P11055
MYH3	XM_011523871.3 link	c.5796+31_5796+32delCC	intron_variant	Intron 40 of 40		XP_011522173.1	P11055
MYH3	XM_047436127.1 link	c.5796+31_5796+32delCC	intron_variant	Intron 42 of 42		XP_047292083.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH3	ENST00000583535.6 link	c.5796+31_5796+32delCC	intron_variant	Intron 40 of 40	5	NM_002470.4	ENSP00000464317.1	P11055
MYH3	ENST00000577963.1 link	n.338+31_338+32delCC	intron_variant	Intron 1 of 1	2
MYH3	ENST00000579928.2 link	n.326+31_326+32delCC	intron_variant	Intron 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

151664

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00290

Gnomad SAS

AF:

0.000416

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000480

GnomAD2 exomes

AF:

0.000114

AC:

AN:

237438

AF XY:

0.000109

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000707

AC:

101

AN:

1428746

Hom.:

AF XY:

0.0000731

AC XY:

AN XY:

710904

show subpopulations

Gnomad4 AFR exome

AF:

0.00

AC:

AN:

31820

Gnomad4 AMR exome

AF:

0.00

AC:

AN:

43776

Gnomad4 ASJ exome

AF:

0.00

AC:

AN:

25564

Gnomad4 EAS exome

AF:

0.000733

AC:

AN:

38224

Gnomad4 SAS exome

AF:

0.000464

AC:

AN:

84102

Gnomad4 FIN exome

AF:

0.00

AC:

AN:

52060

Gnomad4 NFE exome

AF:

0.00000183

AC:

AN:

1090260

Gnomad4 Remaining exome

AF:

0.000545

AC:

AN:

58762

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000171

AC:

AN:

151776

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74222

show subpopulations

Gnomad4 AFR

AF:

0.00

AC:

AN:

Gnomad4 AMR

AF:

0.00

AC:

AN:

Gnomad4 ASJ

AF:

0.00

AC:

AN:

Gnomad4 EAS

AF:

0.00291

AC:

0.00290923

AN:

0.00290923

Gnomad4 SAS

AF:

0.000417

AC:

0.000416667

AN:

0.000416667

Gnomad4 FIN

AF:

0.00

AC:

AN:

Gnomad4 NFE

AF:

0.00

AC:

AN:

Gnomad4 OTH

AF:

0.00427

AC:

0.0042735

AN:

0.0042735

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over