rs200605472
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1
This summary comes from the ClinGen Evidence Repository: The filtering allele frequency (the lower threshold of the 95% CI of 41/10294) of the c.9998G>A (p.Arg3333Gln) variant in the MYO15A gene is 0.302% for Ashkenazi Jewish chromosomes by gnomAD, which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BS1). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1. LINK:https://erepo.genome.network/evrepo/ui/classification/CA177281/MONDO:0019497/005
Frequency
Consequence
NM_016239.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.9998G>A | p.Arg3333Gln | missense_variant | Exon 62 of 66 | ENST00000647165.2 | NP_057323.3 | |
MYO15A | XM_017024715.3 | c.10001G>A | p.Arg3334Gln | missense_variant | Exon 60 of 64 | XP_016880204.1 | ||
MYO15A | XM_017024714.3 | c.9938G>A | p.Arg3313Gln | missense_variant | Exon 59 of 63 | XP_016880203.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000269 AC: 41AN: 152246Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.000274 AC: 66AN: 240818Hom.: 0 AF XY: 0.000281 AC XY: 37AN XY: 131774
GnomAD4 exome AF: 0.000240 AC: 348AN: 1451708Hom.: 2 Cov.: 32 AF XY: 0.000227 AC XY: 164AN XY: 722616
GnomAD4 genome AF: 0.000269 AC: 41AN: 152246Hom.: 0 Cov.: 34 AF XY: 0.000215 AC XY: 16AN XY: 74382
ClinVar
Submissions by phenotype
not provided Benign:2
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not specified Benign:1
p.Arg3333Gln in exon 62 of MYO15A: This variant is not expected to have clinical significance due to a lack of conservation across species, including mammals. O f note, many species, including other primates, have a glutamine (Gln) at this p osition despite high nearby amino acid conservation. This variant has been ident ified in 28/64402 European chromosomes by the Exome Aggregation Consortium (ExAC , http://exac.broadinstitute.org; dbSNP rs200605472). -
MYO15A-related disorder Benign:1
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). -
Nonsyndromic genetic hearing loss Benign:1
The filtering allele frequency (the lower threshold of the 95% CI of 41/10294) of the c.9998G>A (p.Arg3333Gln) variant in the MYO15A gene is 0.302% for Ashkenazi Jewish chromosomes by gnomAD, which is a high enough frequency to be classified as likely benign based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss variants (BS1). In summary, this variant meets criteria to be classified as likely benign. ACMG/AMP criteria applied, as specified by the Hearing Loss Expert Panel: BS1. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at