rs368148603
Your query was ambiguous. Multiple possible variants found:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 3P and 1B. PM2PP3BP3
The NM_194248.3(OTOF):c.3925_3930delAAGAAG(p.Lys1309_Lys1310del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000621 in 1,609,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
OTOF
NM_194248.3 conservative_inframe_deletion
NM_194248.3 conservative_inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 7.93
Publications
1 publications found
Genes affected
OTOF (HGNC:8515): (otoferlin) Mutations in this gene are a cause of neurosensory nonsyndromic recessive deafness, DFNB9. The short form of the encoded protein has 3 C2 domains, a single carboxy-terminal transmembrane domain found also in the C. elegans spermatogenesis factor FER-1 and human dysferlin, while the long form has 6 C2 domains. The homology suggests that this protein may be involved in vesicle membrane fusion. Several transcript variants encoding multiple isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
OTOF Gene-Disease associations (from GenCC):
- autosomal recessive nonsyndromic hearing loss 9Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
- hearing loss, autosomal recessiveInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
No computational evidence supports a deleterious effect, but strongly conserved according to phyloP
BP3
Nonframeshift variant in repetitive region in NM_194248.3
Transcripts
RefSeq
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|
| OTOF | NM_194248.3 | c.3925_3930delAAGAAG | p.Lys1309_Lys1310del | conservative_inframe_deletion | Exon 32 of 47 | ENST00000272371.7 | NP_919224.1 | |
| OTOF | NM_194323.3 | c.1624_1629delAAGAAG | p.Lys542_Lys543del | conservative_inframe_deletion | Exon 15 of 29 | ENST00000339598.8 | NP_919304.1 |
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| OTOF | ENST00000272371.7 | c.3925_3930delAAGAAG | p.Lys1309_Lys1310del | conservative_inframe_deletion | Exon 32 of 47 | 1 | NM_194248.3 | ENSP00000272371.2 | ||
| OTOF | ENST00000339598.8 | c.1624_1629delAAGAAG | p.Lys542_Lys543del | conservative_inframe_deletion | Exon 15 of 29 | 1 | NM_194323.3 | ENSP00000344521.3 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 151970Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
151970
Hom.:
Cov.:
33
Gnomad AFR
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Gnomad OTH
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GnomAD2 exomes AF: 0.00000806 AC: 2AN: 248192 AF XY: 0.00000745 show subpopulations
GnomAD2 exomes
AF:
AC:
2
AN:
248192
AF XY:
Gnomad AFR exome
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GnomAD4 exome AF: 0.00000617 AC: 9AN: 1457550Hom.: 0 AF XY: 0.00000827 AC XY: 6AN XY: 725280 show subpopulations
GnomAD4 exome
AF:
AC:
9
AN:
1457550
Hom.:
AF XY:
AC XY:
6
AN XY:
725280
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33368
American (AMR)
AF:
AC:
0
AN:
44714
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26126
East Asian (EAS)
AF:
AC:
0
AN:
39668
South Asian (SAS)
AF:
AC:
3
AN:
86170
European-Finnish (FIN)
AF:
AC:
0
AN:
53264
Middle Eastern (MID)
AF:
AC:
1
AN:
5756
European-Non Finnish (NFE)
AF:
AC:
4
AN:
1108260
Other (OTH)
AF:
AC:
0
AN:
60224
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
1
1
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0.00
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0.95
Allele balance
Age Distribution
Exome Het
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Age
GnomAD4 genome 0.00000658 AC: 1AN: 151970Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74212 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
151970
Hom.:
Cov.:
33
AF XY:
AC XY:
0
AN XY:
74212
show subpopulations
African (AFR)
AF:
AC:
1
AN:
41386
American (AMR)
AF:
AC:
0
AN:
15260
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3462
East Asian (EAS)
AF:
AC:
0
AN:
5174
South Asian (SAS)
AF:
AC:
0
AN:
4804
European-Finnish (FIN)
AF:
AC:
0
AN:
10586
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67980
Other (OTH)
AF:
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.525
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive nonsyndromic hearing loss 9 Uncertain:1
Feb 28, 2023
Department of Pathology and Laboratory Medicine, Sinai Health System
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:research
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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