NM_016239.4:c.8602-8_8602-5delTGAC
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_016239.4(MYO15A):c.8602-8_8602-5delTGAC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000806 in 1,613,524 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on 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
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYO15A | NM_016239.4 | c.8602-8_8602-5delTGAC | splice_region_variant, intron_variant | Intron 48 of 65 | ENST00000647165.2 | NP_057323.3 | ||
MYO15A | XM_017024715.3 | c.8605-8_8605-5delTGAC | splice_region_variant, intron_variant | Intron 46 of 63 | XP_016880204.1 | |||
MYO15A | XM_017024714.3 | c.8542-8_8542-5delTGAC | splice_region_variant, intron_variant | Intron 45 of 62 | XP_016880203.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000138 AC: 21AN: 152226Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000169 AC: 42AN: 249212Hom.: 0 AF XY: 0.000163 AC XY: 22AN XY: 135332
GnomAD4 exome AF: 0.0000746 AC: 109AN: 1461298Hom.: 0 AF XY: 0.0000702 AC XY: 51AN XY: 727008
GnomAD4 genome AF: 0.000138 AC: 21AN: 152226Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74372
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.8602-8_8602-5delTGAC variant in MYO15A has now been identified by our labo ratory in two individuals with hearing loss, neither of whom had a second MYO15A variant. This variant has also been identified in 17/66206 of European chromoso mes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; d bSNP rs374176599). Although this variant has been seen in the general population , its frequency is not high enough to rule out a pathogenic role. This variant i s located in the 3' splice region. Computational tools do not suggest an impact to splicing; however, this information is not predictive enough to rule out path ogenicity. In summary, the clinical significance of the c.8602-8_8602-5delTGAC v ariant is uncertain. -
not provided Benign:1
- -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at