rs752773977
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP5
The NM_016239.4(MYO15A):c.8340+5G>A variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00000186 in 1,613,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_016239.4 splice_region, intron
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.8340+5G>A | splice_region_variant, intron_variant | ENST00000647165.2 | NP_057323.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYO15A | ENST00000647165.2 | c.8340+5G>A | splice_region_variant, intron_variant | NM_016239.4 | ENSP00000495481.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 249204Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135292
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461634Hom.: 0 Cov.: 34 AF XY: 0.00000275 AC XY: 2AN XY: 727140
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74330
ClinVar
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 3 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Molecular Diagnosis Center for Deafness | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 09, 2016 | Variant classified as Uncertain Significance - Favor Pathogenic. The c.8340+5G>A variant in MYO15A has not been previously reported in individuals with hearing loss. This variant was identified in 1/66250 European chromosomes and in 1/1650 4 South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs752773977). This variant is located in the 5' splic e region. Computational tools suggest an impact to splicing. However, this infor mation is not predictive enough to determine pathogenicity. In summary, while th ere is some suspicion for a pathogenic role, the clinical significance of the c. 8340+5G>A variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at