chr11-77162914-T-TC
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000260.4(MYO7A):c.1623dup(p.Lys542GlnfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,612,458 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. I539I) 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.1623dup | p.Lys542GlnfsTer5 | frameshift_variant | 14/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.1623dup | p.Lys542GlnfsTer5 | frameshift_variant | 14/49 | 1 | NM_000260.4 | ||
MYO7A | ENST00000409619.6 | c.1590dup | p.Lys531GlnfsTer5 | frameshift_variant | 15/50 | 1 | |||
MYO7A | ENST00000458637.6 | c.1623dup | p.Lys542GlnfsTer5 | frameshift_variant | 14/49 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000199 AC: 3AN: 150744Hom.: 0 Cov.: 31
GnomAD4 exome AF: 0.0000417 AC: 61AN: 1461600Hom.: 0 Cov.: 31 AF XY: 0.0000481 AC XY: 35AN XY: 727084
GnomAD4 genome ? AF: 0.0000199 AC: 3AN: 150858Hom.: 0 Cov.: 31 AF XY: 0.0000136 AC XY: 1AN XY: 73698
ClinVar
Submissions by phenotype
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jan 09, 2024 | This sequence change creates a premature translational stop signal (p.Lys542Glnfs*5) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is present in population databases (rs782077721, gnomAD 0.005%). This premature translational stop signal has been observed in individuals with autosomal recessive MYO7A-related disease (PMID: 10930322, 27743452, 30459346). ClinVar contains an entry for this variant (Variation ID: 521129). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2021 | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 33576163, 10930322, 27743452) - |
Inborn genetic diseases Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 22, 2016 | - - |
Usher syndrome type 1B Pathogenic:1
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Usher syndrome type 1 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals | Feb 01, 2019 | - - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Blueprint Genetics | Sep 19, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at