rs773489275
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_016239.4(MYO15A):c.9328C>T(p.Arg3110Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000273 in 1,613,890 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 Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R3110Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_016239.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.9328C>T | p.Arg3110Trp | missense_variant | 56/66 | ENST00000647165.2 | |
MYO15A | XM_017024715.3 | c.9331C>T | p.Arg3111Trp | missense_variant | 54/64 | ||
MYO15A | XM_017024714.3 | c.9268C>T | p.Arg3090Trp | missense_variant | 53/63 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.9328C>T | p.Arg3110Trp | missense_variant | 56/66 | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249354Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135290
GnomAD4 exome AF: 0.0000287 AC: 42AN: 1461770Hom.: 0 Cov.: 32 AF XY: 0.0000206 AC XY: 15AN XY: 727184
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74310
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 28, 2017 | The p.Arg3110Trp variant in MYO15A has not been previously reported in individua ls with hearing loss, but has been identified in 1/16102 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSN P rs773489275). Although this variant has been seen in the general population, i ts frequency is not high enough to rule out a pathogenic role. Computational pre diction tools and conservation analysis suggest that the p.Arg3110Trp variant ma y impact the protein, though this information is not predictive enough to determ ine pathogenicity. In summary, the clinical significance of the p.Arg3110Trp var iant is uncertain. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 31, 2022 | The c.9328C>T (p.R3110W) alteration is located in exon 56 (coding exon 55) of the MYO15A gene. This alteration results from a C to T substitution at nucleotide position 9328, causing the arginine (R) at amino acid position 3110 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at