rs1233700794
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PM4_Supporting
The NM_004999.4(MYO6):c.1884_1886delCAA(p.Asn628del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.00000682 in 1,613,792 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000068 ( 0 hom. )
Consequence
MYO6
NM_004999.4 disruptive_inframe_deletion
NM_004999.4 disruptive_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 5.68
Genes affected
MYO6 (HGNC:7605): (myosin VI) This gene encodes a reverse-direction motor protein that moves toward the minus end of actin filaments and plays a role in intracellular vesicle and organelle transport. The protein consists of a motor domain containing an ATP- and an actin-binding site and a globular tail which interacts with other proteins. This protein maintains the structural integrity of inner ear hair cells and mutations in this gene cause non-syndromic autosomal dominant and recessive hearing loss. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 1 ACMG points.
PM4
Nonframeshift variant in NON repetitive region in NM_004999.4. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 33
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GnomAD4 exome AF: 0.00000684 AC: 10AN: 1461664Hom.: 0 AF XY: 0.00000688 AC XY: 5AN XY: 727136
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74324
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 04, 2016 | The p.Asn628del variant in MYO6 has not been previously reported in individuals with hearing loss or in large population studies. This variant is a deletion of 1 amino acid at position 628 and is not predicted to alter the protein reading-f rame. It is unclear if this deletion will impact the protein function. In summar y, the clinical significance of the p.Asn628del variant is uncertain. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at