rs112859834
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_002472.3(MYH8):c.5463+20T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,614,124 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0024 ( 2 hom., cov: 32)
Exomes 𝑓: 0.00025 ( 3 hom. )
Consequence
MYH8
NM_002472.3 intron
NM_002472.3 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.697
Genes affected
MYH8 (HGNC:7578): (myosin heavy chain 8) Myosins are actin-based motor proteins that function in the generation of mechanical force in eukaryotic cells. Muscle myosins are heterohexamers composed of 2 myosin heavy chains and 2 pairs of nonidentical myosin light chains. This gene encodes a member of the class II or conventional myosin heavy chains, and functions in skeletal muscle contraction. This gene is predominantly expressed in fetal skeletal muscle. This gene is found in a cluster of myosin heavy chain genes on chromosome 17. A mutation in this gene results in trismus-pseudocamptodactyly syndrome. [provided by RefSeq, Sep 2009]
MYHAS (HGNC:50609): (myosin heavy chain gene cluster antisense RNA) Predicted to enable primary miRNA binding activity. Predicted to be involved in response to muscle activity and skeletal muscle fiber development. Predicted to act upstream of or within with a positive effect on gene expression. Predicted to be located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 17-10392811-A-G is Benign according to our data. Variant chr17-10392811-A-G is described in ClinVar as [Benign]. Clinvar id is 258721.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High AC in GnomAd4 at 361 AD gene.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYH8 | ENST00000403437.2 | c.5463+20T>C | intron_variant | 5 | NM_002472.3 | ENSP00000384330.2 | ||||
ENSG00000272736 | ENST00000399342.6 | n.76+9604A>G | intron_variant | 3 | ||||||
ENSG00000272736 | ENST00000581304.1 | n.52+9604A>G | intron_variant | 3 | ||||||
MYHAS | ENST00000587182.2 | n.64+9604A>G | intron_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00237 AC: 360AN: 152112Hom.: 2 Cov.: 32
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GnomAD3 exomes AF: 0.000581 AC: 146AN: 251490Hom.: 0 AF XY: 0.000375 AC XY: 51AN XY: 135918
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GnomAD4 exome AF: 0.000252 AC: 368AN: 1461894Hom.: 3 Cov.: 33 AF XY: 0.000223 AC XY: 162AN XY: 727248
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GnomAD4 genome AF: 0.00237 AC: 361AN: 152230Hom.: 2 Cov.: 32 AF XY: 0.00222 AC XY: 165AN XY: 74440
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at