rs747721069
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016239.4(MYO15A):āc.754C>Gā(p.His252Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000678 in 1,607,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. H252H) has been classified as Likely benign.
Frequency
Consequence
NM_016239.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.754C>G | p.His252Asp | missense_variant | 2/66 | ENST00000647165.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.754C>G | p.His252Asp | missense_variant | 2/66 | NM_016239.4 | P1 | ||
MYO15A | ENST00000583079.1 | n.387C>G | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152086Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000246 AC: 6AN: 243686Hom.: 0 AF XY: 0.0000300 AC XY: 4AN XY: 133202
GnomAD4 exome AF: 0.0000715 AC: 104AN: 1455484Hom.: 0 Cov.: 35 AF XY: 0.0000801 AC XY: 58AN XY: 724276
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152086Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74284
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 | Aug 10, 2017 | The p.His252Asp variant in MYO15A has not been previously reported in individual s with hearing loss but has been identified 4/33544 Latino chromosomes by the Ge nome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs747 721069). Computational prediction tools and conservation analysis suggest that t he p.His252Asp variant may not impact the protein, though this information is no t predictive enough to rule out pathogenicity. In summary, the clinical signific ance of the p.His252Asp variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 09, 2022 | This sequence change replaces histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 252 of the MYO15A protein (p.His252Asp). This variant is present in population databases (rs747721069, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYO15A-related conditions. ClinVar contains an entry for this variant (Variation ID: 517513). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYO15A protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at