rs531034566
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong
The NM_194248.3(OTOF):c.80-5C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000645 in 1,550,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_194248.3 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -10 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.80-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000272371.7 | |||
OTOF | NM_001287489.2 | c.80-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.80-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_194248.3 | A1 | |||
OTOF | ENST00000403946.7 | c.80-5C>T | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 5 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000355 AC: 54AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000946 AC: 15AN: 158556Hom.: 0 AF XY: 0.0000720 AC XY: 6AN XY: 83388
GnomAD4 exome AF: 0.0000329 AC: 46AN: 1398658Hom.: 0 Cov.: 30 AF XY: 0.0000304 AC XY: 21AN XY: 690096
GnomAD4 genome ? AF: 0.000355 AC: 54AN: 152268Hom.: 0 Cov.: 33 AF XY: 0.000309 AC XY: 23AN XY: 74450
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 04, 2016 | c.80-5C>T in intron 1 of OTOF: This variant is not expected to have clinical sig nificance because a C>T change at this position does not diverge from the splice consensus sequence and is therefore unlikely to impact splicing. It has been id entified in 1/2848 of African chromosomes by the Exome Aggregation Consortium (E xAC, http://exac.broadinstitute.org; dbSNP rs531034566). - |
OTOF-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 02, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at