rs376535635
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_000260.4(MYO7A):c.3262C>T(p.Gln1088Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000248 in 1,612,966 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 Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. Q1088Q) 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.3262C>T | p.Gln1088Ter | stop_gained | 25/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.3262C>T | p.Gln1088Ter | stop_gained | 25/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248158Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135026
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1460772Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 726636
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152194Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74352
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 2 Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | The Shared Resource Centre "Genome", Research Centre for Medical Genetics | Nov 10, 2022 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 02, 2016 | - - |
Usher syndrome type 1 Pathogenic:2
Pathogenic, no assertion criteria provided | research | Sharon lab, Hadassah-Hebrew University Medical Center | Jun 23, 2019 | - - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Nov 02, 2016 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 16, 2023 | This sequence change creates a premature translational stop signal (p.Gln1088*) 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 (rs376535635, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with deafness, inherited retinal disease, and/or Usher syndrome (PMID: 23591405, 30358468, 31456290, 32860223). ClinVar contains an entry for this variant (Variation ID: 371695). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at