rs397750512
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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
NM_002470.4 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -2.63
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]
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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 |
---|---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.5457+9_5457+10insA | intron_variant | ENST00000583535.6 | NP_002461.2 | |||
MYH3 | XM_011523870.4 | c.5457+9_5457+10insA | intron_variant | XP_011522172.1 | ||||
MYH3 | XM_011523871.3 | c.5457+9_5457+10insA | intron_variant | XP_011522173.1 | ||||
MYH3 | XM_047436127.1 | c.5457+9_5457+10insA | intron_variant | XP_047292083.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH3 | ENST00000583535.6 | c.5457+9_5457+10insA | intron_variant | 5 | NM_002470.4 | ENSP00000464317 | P1 |
Frequencies
GnomAD3 genomes AF: 0.590 AC: 89619AN: 151876Hom.: 29259 Cov.: 0
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GnomAD3 exomes AF: 0.647 AC: 162805AN: 251468Hom.: 54778 AF XY: 0.655 AC XY: 88966AN XY: 135900
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GnomAD4 exome AF: 0.699 AC: 1021853AN: 1461886Hom.: 363174 Cov.: 35 AF XY: 0.697 AC XY: 507033AN XY: 727240
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GnomAD4 genome AF: 0.590 AC: 89638AN: 151994Hom.: 29258 Cov.: 0 AF XY: 0.588 AC XY: 43678AN XY: 74310
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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 submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 26, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Freeman-Sheldon syndrome Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Feb 01, 2024 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | May 27, 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 | - - |
Arthrogryposis multiplex congenita Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jun 14, 2016 | - - |
Contractures, pterygia, and spondylocarpotarsal fusion syndrome 1A Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 05, 2021 | - - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at