rs111033187
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000260.4(MYO7A):c.397del(p.His133ThrfsTer13) variant causes a frameshift change. The variant allele was found at a frequency of 0.000000684 in 1,461,398 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. P131P) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000260.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.397del | p.His133ThrfsTer13 | frameshift_variant | 5/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.397del | p.His133ThrfsTer13 | frameshift_variant | 5/49 | 1 | NM_000260.4 | ||
MYO7A | ENST00000458637.6 | c.397del | p.His133ThrfsTer13 | frameshift_variant | 5/49 | 1 | P1 | ||
MYO7A | ENST00000409619.6 | c.364del | p.His122ThrfsTer13 | frameshift_variant | 6/50 | 1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461398Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726964
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen | Jun 17, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2019 | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant has not been reported in the literature in individuals with MYO7A-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.His133Thrfs*13) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at