rs373295633
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_016239.4(MYO15A):c.9812G>A(p.Arg3271His) variant causes a missense change. The variant allele was found at a frequency of 0.0000347 in 1,613,452 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R3271C) has been classified as Uncertain significance.
Frequency
Consequence
NM_016239.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.9812G>A | p.Arg3271His | missense_variant | 61/66 | ENST00000647165.2 | |
MYO15A | XM_017024715.3 | c.9815G>A | p.Arg3272His | missense_variant | 59/64 | ||
MYO15A | XM_017024714.3 | c.9752G>A | p.Arg3251His | missense_variant | 58/63 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.9812G>A | p.Arg3271His | missense_variant | 61/66 | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248928Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 135096
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461250Hom.: 0 Cov.: 32 AF XY: 0.0000344 AC XY: 25AN XY: 726926
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152202Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74366
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 | Sep 09, 2014 | The Arg3271His variant in MYO15A has not been previously reported in individuals with hearing loss, but has been identified 1/4142 of African American chromosom es by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbS NP rs373295633). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Arginine (Arg) at position 3271 is not conserved in mammals or evolutionarily distant species, raising the possibility that a change at this position may be tolerated. Addit ional computational prediction tools do not provide strong support for or agains t an impact to the protein. In summary, the clinical significance of the Arg3271 His variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 10, 2022 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at