NM_194323.3:c.3678G>T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_194323.3(OTOF):c.3678G>T(p.Lys1226Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,424 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_194323.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000339598.8 | c.3678G>T | p.Lys1226Asn | missense_variant | Exon 29 of 29 | 1 | NM_194323.3 | ENSP00000344521.3 | ||
OTOF | ENST00000272371 | c.*183G>T | 3_prime_UTR_variant | Exon 47 of 47 | 1 | NM_194248.3 | ENSP00000272371.2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000798 AC: 2AN: 250658Hom.: 0 AF XY: 0.00000738 AC XY: 1AN XY: 135432
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461424Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 726930
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Variant summary: OTOF c.*183G>T is located in the untranslated mRNA region downstream of the termination codon. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250658 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.*183G>T (also known as c.5979G>T) has been reported in the literature in individuals affected with auditory neuropathy spectrum disorder (Example: Thorpe_2021). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 34424407). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at