rs397750512

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_002470.4(MYH3):​c.5457+9_5457+10insA 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 1,613,880 control chromosomes in the GnomAD database, including 392,432 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.59 ( 29258 hom., cov: 0)
Exomes 𝑓: 0.70 ( 363174 hom. )

Consequence

MYH3
NM_002470.4 intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -2.63
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6
Variant 17-10630278-C-CT is Benign according to our data. Variant chr17-10630278-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 258698.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 HGVSp Effect #exon/exons MANE Protein UniProt
MYH3NM_002470.4 linkuse as main transcriptc.5457+9_5457+10insA intron_variant ENST00000583535.6 NP_002461.2
MYH3XM_011523870.4 linkuse as main transcriptc.5457+9_5457+10insA intron_variant XP_011522172.1
MYH3XM_011523871.3 linkuse as main transcriptc.5457+9_5457+10insA intron_variant XP_011522173.1
MYH3XM_047436127.1 linkuse as main transcriptc.5457+9_5457+10insA intron_variant XP_047292083.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MYH3ENST00000583535.6 linkuse as main transcriptc.5457+9_5457+10insA intron_variant 5 NM_002470.4 ENSP00000464317 P1

Frequencies

GnomAD3 genomes
AF:
0.590
AC:
89619
AN:
151876
Hom.:
29259
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.297
Gnomad AMI
AF:
0.743
Gnomad AMR
AF:
0.619
Gnomad ASJ
AF:
0.711
Gnomad EAS
AF:
0.522
Gnomad SAS
AF:
0.537
Gnomad FIN
AF:
0.741
Gnomad MID
AF:
0.547
Gnomad NFE
AF:
0.739
Gnomad OTH
AF:
0.604
GnomAD3 exomes
AF:
0.647
AC:
162805
AN:
251468
Hom.:
54778
AF XY:
0.655
AC XY:
88966
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.295
Gnomad AMR exome
AF:
0.595
Gnomad ASJ exome
AF:
0.715
Gnomad EAS exome
AF:
0.520
Gnomad SAS exome
AF:
0.552
Gnomad FIN exome
AF:
0.747
Gnomad NFE exome
AF:
0.733
Gnomad OTH exome
AF:
0.677
GnomAD4 exome
AF:
0.699
AC:
1021853
AN:
1461886
Hom.:
363174
Cov.:
35
AF XY:
0.697
AC XY:
507033
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.278
Gnomad4 AMR exome
AF:
0.602
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:
0.590
AC:
89638
AN:
151994
Hom.:
29258
Cov.:
0
AF XY:
0.588
AC XY:
43678
AN XY:
74310
show subpopulations
Gnomad4 AFR
AF:
0.297
Gnomad4 AMR
AF:
0.620
Gnomad4 ASJ
AF:
0.711
Gnomad4 EAS
AF:
0.522
Gnomad4 SAS
AF:
0.536
Gnomad4 FIN
AF:
0.741
Gnomad4 NFE
AF:
0.739
Gnomad4 OTH
AF:
0.604
Alfa
AF:
0.680
Hom.:
8115
Bravo
AF:
0.567
Asia WGS
AF:
0.513
AC:
1790
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:11
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:3
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesMar 26, 2016- -
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, no assertion criteria providedclinical testingClinical Genetics, Academic Medical Center-- -
Freeman-Sheldon syndrome Benign:2
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
not provided Benign:2
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -
Benign, criteria provided, single submitterclinical testingGeneDxMay 27, 2021- -
Contractures, pterygia, and variable skeletal fusions syndrome 1B Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
Arthrogryposis, distal, type 2B3 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -
Arthrogryposis multiplex congenita Benign:1
Likely benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabSep 05, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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.

Other links and lift over

dbSNP: rs397750512; hg19: chr17-10533595; API