rs397516331
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000260.4(MYO7A):c.6498C>A(p.Tyr2166Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000197 in 152,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Y2166Y) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_000260.4 stop_gained
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.6498C>A | p.Tyr2166Ter | stop_gained | 48/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.6498C>A | p.Tyr2166Ter | stop_gained | 48/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152278Hom.: 0 Cov.: 34
GnomAD4 exome Cov.: 37
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152278Hom.: 0 Cov.: 34 AF XY: 0.0000403 AC XY: 3AN XY: 74396
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Mar 02, 2023 | This sequence change creates a premature translational stop signal (p.Tyr2166*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 43330). For these reasons, this variant has been classified as Pathogenic. - |
Rare genetic deafness Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 21, 2011 | The Tyr2166X variant in MYO7A has not been reported in the literature nor previo usly identified by our laboratory. The Tyr2166X variant leads to a premature sto p codon at position 2166, which is predicted to lead to a truncated or absent pr otein. In summary, this variant meets our criteria to be classified as pathogeni c. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at