rs111706333
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_194248.3(OTOF):c.2407-17C>T variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,606,646 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000078 ( 0 hom. )
Consequence
OTOF
NM_194248.3 splice_polypyrimidine_tract, intron
NM_194248.3 splice_polypyrimidine_tract, intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.445
Genes affected
OTOF (HGNC:8515): (otoferlin) Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has 3 C2 domains, a single carboxy-terminal transmembrane domain found also in the C. elegans spermatogenesis factor FER-1 and human dysferlin, while the long form has 6 C2 domains. The homology suggests that this protein may be involved in vesicle membrane fusion. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 2-26477305-G-A is Benign according to our data. Variant chr2-26477305-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 263082.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.2407-17C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000272371.7 | NP_919224.1 | |||
OTOF | NM_194323.3 | c.166-17C>T | splice_polypyrimidine_tract_variant, intron_variant | ENST00000339598.8 | NP_919304.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.2407-17C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_194248.3 | ENSP00000272371 | A1 | |||
OTOF | ENST00000339598.8 | c.166-17C>T | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_194323.3 | ENSP00000344521 |
Frequencies
GnomAD3 genomes AF: 0.000506 AC: 77AN: 152192Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000142 AC: 34AN: 239636Hom.: 0 AF XY: 0.000161 AC XY: 21AN XY: 130444
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GnomAD4 exome AF: 0.0000784 AC: 114AN: 1454336Hom.: 0 Cov.: 32 AF XY: 0.0000830 AC XY: 60AN XY: 723202
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GnomAD4 genome AF: 0.000545 AC: 83AN: 152310Hom.: 0 Cov.: 32 AF XY: 0.000524 AC XY: 39AN XY: 74478
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 14, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at