rs876657898
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PM4
The NM_016239.4(MYO15A):c.349_357delTACGGCCGC(p.Tyr117_Arg119del) variant causes a conservative inframe deletion change. The variant allele was found at a frequency of 0.000855 in 1,611,294 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_016239.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.349_357delTACGGCCGC | p.Tyr117_Arg119del | conservative_inframe_deletion | Exon 2 of 66 | NM_016239.4 | ENSP00000495481.1 | |||
MYO15A | ENST00000583079.1 | n.-21_-13delGCTACGGCC | upstream_gene_variant | 6 |
Frequencies
GnomAD3 genomes AF: 0.000598 AC: 91AN: 152196Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000495 AC: 117AN: 236402Hom.: 0 AF XY: 0.000512 AC XY: 67AN XY: 130974
GnomAD4 exome AF: 0.000881 AC: 1286AN: 1458980Hom.: 1 AF XY: 0.000880 AC XY: 639AN XY: 725792
GnomAD4 genome AF: 0.000597 AC: 91AN: 152314Hom.: 0 Cov.: 33 AF XY: 0.000591 AC XY: 44AN XY: 74472
ClinVar
Submissions by phenotype
not provided Uncertain:5
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This variant, c.349_357del, results in the deletion of 3 amino acid(s) of the MYO15A protein (p.Tyr117_Arg119del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs752352091, gnomAD 0.09%), and has an allele count higher than expected for a pathogenic variant. 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: 228948). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
The p.Tyr117_Arg119del variant in MYO15A has been previously reported by our laboratory in 1 individual with hearing loss, and has also been identified in 0.08% (103/120036) of European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is a deletion of three amino acids at positions 117 to 119 and is not predicted to alter the protein reading-frame of the gene. It is unclear if this deletion will impact the protein function. In summary, the clinical significance of the p.Tyr117_Arg119del variant is uncertain. ACMG/AMP Criteria applied: BS1_Supporting. -
In-frame deletion of 3 amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
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Autosomal recessive nonsyndromic hearing loss 3 Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at