chr2-26464041-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_194248.3(OTOF):c.5026C>T(p.Arg1676Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000835 in 1,613,656 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_194248.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.5026C>T | p.Arg1676Cys | missense_variant | Exon 40 of 47 | 1 | NM_194248.3 | ENSP00000272371.2 | ||
OTOF | ENST00000339598.8 | c.2725C>T | p.Arg909Cys | missense_variant | Exon 23 of 29 | 1 | NM_194323.3 | ENSP00000344521.3 |
Frequencies
GnomAD3 genomes AF: 0.000867 AC: 132AN: 152164Hom.: 4 Cov.: 32
GnomAD3 exomes AF: 0.00144 AC: 362AN: 250878Hom.: 6 AF XY: 0.00137 AC XY: 186AN XY: 135746
GnomAD4 exome AF: 0.000832 AC: 1216AN: 1461374Hom.: 18 Cov.: 32 AF XY: 0.000799 AC XY: 581AN XY: 727004
GnomAD4 genome AF: 0.000860 AC: 131AN: 152282Hom.: 4 Cov.: 32 AF XY: 0.00106 AC XY: 79AN XY: 74462
ClinVar
Submissions by phenotype
not provided Benign:2
This variant is associated with the following publications: (PMID: 21935370, 22575033, 24053799, 28335750, 22906306, 26346818, 30245029, 33095980) -
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Autosomal recessive nonsyndromic hearing loss 9 Benign:2
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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not specified Benign:1
Arg1676Cys in exon 40 of OTOF: This variant has been reported in two individuals with hearing loss (Isawa 2013, Wang 2011) but it is not expected to have clinic al significance because it has been seen in 1.6% (9/572) of Asian chromosomes by the 1000 Genomes Project (dbSNP rs139767460), with the frequency in Japanese ch romosomes in particular being 3.4% (6/178). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at