chr11-77192104-C-A
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_000260.4(MYO7A):c.3978C>A(p.Cys1326Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,534 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. C1326C) 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 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO7A | NM_000260.4 | c.3978C>A | p.Cys1326Ter | stop_gained | 31/49 | ENST00000409709.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO7A | ENST00000409709.9 | c.3978C>A | p.Cys1326Ter | stop_gained | 31/49 | 1 | NM_000260.4 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248256Hom.: 0 AF XY: 0.00000742 AC XY: 1AN XY: 134828
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461534Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727034
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 25, 2023 | For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with deafness (PMID: 27344577). This variant is present in population databases (rs111033376, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Cys1326*) 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at