2-26460846-G-C
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_194248.3(OTOF):c.5712+6C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000824 in 1,613,942 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_194248.3 splice_region, intron
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.5712+6C>G | splice_region_variant, intron_variant | Intron 44 of 46 | ENST00000272371.7 | NP_919224.1 | ||
OTOF | NM_194323.3 | c.3411+6C>G | splice_region_variant, intron_variant | Intron 27 of 28 | ENST00000339598.8 | NP_919304.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.5712+6C>G | splice_region_variant, intron_variant | Intron 44 of 46 | 1 | NM_194248.3 | ENSP00000272371.2 | |||
OTOF | ENST00000339598.8 | c.3411+6C>G | splice_region_variant, intron_variant | Intron 27 of 28 | 1 | NM_194323.3 | ENSP00000344521.3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152092Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251354Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135870
GnomAD4 exome AF: 0.0000896 AC: 131AN: 1461850Hom.: 0 Cov.: 35 AF XY: 0.0000743 AC XY: 54AN XY: 727234
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152092Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74292
ClinVar
Submissions by phenotype
not provided Uncertain:1
This sequence change falls in intron 44 of the OTOF gene. It does not directly change the encoded amino acid sequence of the OTOF protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs200435099, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with OTOF-related conditions. ClinVar contains an entry for this variant (Variation ID: 48267). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. -
not specified Benign:1
5712+6C>G in OTOF: This variant is not expected to have clinical significance be cause 5 splice assessment tools do not suggest an impact to splicing. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at