rs546575046
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_016239.4(MYO15A):c.10136C>A(p.Ser3379Ter) variant causes a stop gained change. The variant allele was found at a frequency of 0.00000137 in 1,460,972 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. S3379S) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_016239.4 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 |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.10136C>A | p.Ser3379Ter | stop_gained | 63/66 | ENST00000647165.2 | |
MYO15A | XM_017024715.3 | c.10139C>A | p.Ser3380Ter | stop_gained | 61/64 | ||
MYO15A | XM_017024714.3 | c.10076C>A | p.Ser3359Ter | stop_gained | 60/63 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.10136C>A | p.Ser3379Ter | stop_gained | 63/66 | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1460972Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726836
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Rare genetic deafness Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 23, 2013 | The Ser3379X variant in MYO15A has not been reported in individuals with hearing loss. This nonsense variant leads to a premature termination codon at position 3379, which is predicted to lead to a truncated or absent protein. In summary, t his variant meets our criteria to be classified as pathogenic (http://pcpgm.part ners.org/LMM). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at