rs200041829
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_016239.4(MYO15A):āc.5803C>Gā(p.Arg1935Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000694 in 1,612,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1935L) 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_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.5803C>G | p.Arg1935Gly | missense_variant | 24/66 | ENST00000647165.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.5803C>G | p.Arg1935Gly | missense_variant | 24/66 | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000788 AC: 12AN: 152246Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000157 AC: 39AN: 248402Hom.: 0 AF XY: 0.000193 AC XY: 26AN XY: 134936
GnomAD4 exome AF: 0.0000685 AC: 100AN: 1460692Hom.: 0 Cov.: 32 AF XY: 0.0000771 AC XY: 56AN XY: 726644
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152246Hom.: 0 Cov.: 33 AF XY: 0.0000538 AC XY: 4AN XY: 74384
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 | Nov 25, 2015 | The p.Arg1935Gly variant in MYO15A has not been previously reported in individua ls with hearing loss. This variant has been identified in 10/62318 European chro mosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.or g; dbSNP rs200041829); however, this frequency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses do not provide strong evidence for or against an impact to the protein. In summary, th e clinical significance of the p.Arg1935Gly variant is uncertain. - |
MYO15A-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 19, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at