rs56259391
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_002470.4(MYH3):c.2106C>T(p.Gly702=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0415 in 1,613,832 control chromosomes in the GnomAD database, including 1,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.058 ( 402 hom., cov: 32)
Exomes 𝑓: 0.040 ( 1494 hom. )
Consequence
MYH3
NM_002470.4 synonymous
NM_002470.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.879
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 17-10641144-G-A is Benign according to our data. Variant chr17-10641144-G-A is described in ClinVar as [Benign]. Clinvar id is 129648.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-10641144-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-0.879 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.124 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH3 | NM_002470.4 | c.2106C>T | p.Gly702= | synonymous_variant | 19/41 | ENST00000583535.6 | |
MYH3 | XM_011523870.4 | c.2106C>T | p.Gly702= | synonymous_variant | 19/41 | ||
MYH3 | XM_011523871.3 | c.2106C>T | p.Gly702= | synonymous_variant | 19/41 | ||
MYH3 | XM_047436127.1 | c.2106C>T | p.Gly702= | synonymous_variant | 21/43 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH3 | ENST00000583535.6 | c.2106C>T | p.Gly702= | synonymous_variant | 19/41 | 5 | NM_002470.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0583 AC: 8873AN: 152126Hom.: 402 Cov.: 32
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GnomAD3 exomes AF: 0.0388 AC: 9752AN: 251444Hom.: 327 AF XY: 0.0383 AC XY: 5207AN XY: 135896
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GnomAD4 exome AF: 0.0398 AC: 58099AN: 1461588Hom.: 1494 Cov.: 38 AF XY: 0.0397 AC XY: 28851AN XY: 727122
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GnomAD4 genome ? AF: 0.0583 AC: 8876AN: 152244Hom.: 402 Cov.: 32 AF XY: 0.0563 AC XY: 4193AN XY: 74442
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:4
Benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | - | Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. - |
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 26, 2019 | - - |
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Freeman-Sheldon syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Distal arthrogryposis type 2B1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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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