rs200843771
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_016239.4(MYO15A):āc.10094A>Gā(p.Gln3365Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000762 in 1,613,928 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).
Frequency
Consequence
NM_016239.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.10094A>G | p.Gln3365Arg | missense_variant | 63/66 | ENST00000647165.2 | |
MYO15A | XM_017024715.3 | c.10097A>G | p.Gln3366Arg | missense_variant | 61/64 | ||
MYO15A | XM_017024714.3 | c.10034A>G | p.Gln3345Arg | missense_variant | 60/63 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.10094A>G | p.Gln3365Arg | missense_variant | 63/66 | NM_016239.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000414 AC: 63AN: 152194Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000883 AC: 22AN: 249154Hom.: 0 AF XY: 0.0000665 AC XY: 9AN XY: 135294
GnomAD4 exome AF: 0.0000411 AC: 60AN: 1461616Hom.: 0 Cov.: 32 AF XY: 0.0000316 AC XY: 23AN XY: 727108
GnomAD4 genome ? AF: 0.000414 AC: 63AN: 152312Hom.: 0 Cov.: 32 AF XY: 0.000403 AC XY: 30AN XY: 74488
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Apr 14, 2020 | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 13, 2016 | Variant classified as Uncertain Significance - Favor Benign. The p.Gln3365Arg va riant in MYO15A has not been previously reported in individuals with hearing los s, but it has been identified in 0.1% (12/9576) of African chromosomes by the Ex ome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200843 771). Although this variant has been seen in the general population, its frequen cy is not high enough to rule out a pathogenic role. The glutamine at position 3 365 is not conserved in mammals or evolutionary distant species; with 2 species (elephant and manatee) having an arginine (Arg) at this position supporting that a change at this position may be tolerated. Additional computational prediction tools do not provide strong support for or against an impact to the protein. I n summary, while the clinical significance of the p.Gln3365Arg variant is uncert ain, available data suggest that it is more likely to be benign. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 31, 2020 | The c.10094A>G (p.Q3365R) alteration is located in exon 63 (coding exon 62) of the MYO15A gene. This alteration results from an A to G substitution at nucleotide position 10094, causing the glutamine (Q) at amino acid position 3365 to be replaced by an arginine (R). Based on data from the Genome Aggregation Database (gnomAD) database, the MYO15A c.10094A>G alteration was observed in 0.01% (38/280546) of total alleles studied, with a frequency of 0.15% (37/24164) in the African subpopulation. This amino acid position is well conserved in available vertebrate species. The p.Q3365R alteration is predicted to be tolerated by in silico analysis. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Autosomal recessive nonsyndromic hearing loss 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Oct 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at