rs727505142
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_194248.3(OTOF):āc.3124A>Gā(p.Met1042Val) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.00000868 in 1,612,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/25 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_194248.3 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.3124A>G | p.Met1042Val | missense_variant, splice_region_variant | 25/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.883A>G | p.Met295Val | missense_variant, splice_region_variant | 8/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.3124A>G | p.Met1042Val | missense_variant, splice_region_variant | 25/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.883A>G | p.Met295Val | missense_variant, splice_region_variant | 8/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152106Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 4AN: 250644Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135812
GnomAD4 exome AF: 0.00000616 AC: 9AN: 1460654Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 726638
GnomAD4 genome ? AF: 0.0000328 AC: 5AN: 152224Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74426
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 30, 2015 | proposed classification - variant undergoing re-assessment, contact laboratory - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 10, 2022 | This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1042 of the OTOF protein (p.Met1042Val). This variant is present in population databases (rs727505142, gnomAD 0.02%). 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: 179807). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at