rs374226960
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_017433.5(MYO3A):c.3086A>G(p.Asp1029Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000322 in 1,613,768 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. D1029N) has been classified as Uncertain significance.
Frequency
Consequence
NM_017433.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYO3A | NM_017433.5 | c.3086A>G | p.Asp1029Gly | missense_variant | 27/35 | ENST00000642920.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYO3A | ENST00000642920.2 | c.3086A>G | p.Asp1029Gly | missense_variant | 27/35 | NM_017433.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000328 AC: 5AN: 152218Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000358 AC: 9AN: 251350Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135854
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461550Hom.: 0 Cov.: 30 AF XY: 0.0000344 AC XY: 25AN XY: 727104
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152218Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74376
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 | Dec 19, 2013 | The Asp1029Gly variant in MYO3A has not been previously reported in individuals with hearing loss, but has been identified in 1/8600 European American chromosom es by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu). Comput ational analyses (biochemical amino acid properties, conservation, AlignGVGD, Po lyPhen-2, and SIFT) do not provide strong support for or against an impact to th e protein. This variant may potentially introduce a cryptic 5' splice site, and computational tools suggest an impact to splicing. However, this information is not predictive enough to determine pathogenicity. In summary, additional inform ation is needed to fully assess the clinical significance of this variant. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 26, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1029 of the MYO3A protein (p.Asp1029Gly). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 179490). This variant has not been reported in the literature in individuals affected with MYO3A-related conditions. This variant is present in population databases (rs374226960, gnomAD 0.006%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at