rs727503318
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_016239.4(MYO15A):āc.8404A>Gā(p.Met2802Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.8404A>G | p.Met2802Val | missense_variant | 47/66 | ENST00000647165.2 | NP_057323.3 | |
LOC105371567 | XR_001752809.1 | upstream_gene_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.8404A>G | p.Met2802Val | missense_variant | 47/66 | NM_016239.4 | ENSP00000495481 | P1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000803 AC: 2AN: 249122Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135278
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461444Hom.: 0 Cov.: 34 AF XY: 0.00000550 AC XY: 4AN XY: 727032
GnomAD4 genome Cov.: 33
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 | May 21, 2013 | The Met2802Val variant in MYO15A has not been reported in affected individuals o r in large population studies. Computational analyses (biochemical amino acid pr operties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the variant may not impact the protein, particularly given a lack of amino acid conservatio n at the Met2802 site including a Val residue in another mammal. However, we can not rule out pathogenicity, especially in light of the existing MYO15A variant i dentified. In summary, the clinical significance of this variant cannot be deter mined with certainty. We recommend parental testing to assess cis/trans configur ation with the other MYO15A variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at