rs775320200

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_194248.3(OTOF):​c.*204G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,457,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

OTOF
NM_194248.3 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.636

Publications

0 publications found
Variant links:
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 9
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), G2P
  • hearing loss, autosomal recessive
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
OTOFNM_194248.3 linkc.*204G>T 3_prime_UTR_variant Exon 47 of 47 ENST00000272371.7 NP_919224.1 Q9HC10-1
OTOFNM_194323.3 linkc.*6G>T 3_prime_UTR_variant Exon 29 of 29 ENST00000339598.8 NP_919304.1 Q9HC10-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
OTOFENST00000272371.7 linkc.*204G>T 3_prime_UTR_variant Exon 47 of 47 1 NM_194248.3 ENSP00000272371.2 Q9HC10-1
OTOFENST00000339598.8 linkc.*6G>T 3_prime_UTR_variant Exon 29 of 29 1 NM_194323.3 ENSP00000344521.3 Q9HC10-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD2 exomes
AF:
0.00
AC:
0
AN:
247882
AF XY:
0.00
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457038
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
724140
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33382
American (AMR)
AF:
0.00
AC:
0
AN:
44524
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25820
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39650
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85856
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53102
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5724
European-Non Finnish (NFE)
AF:
9.02e-7
AC:
1
AN:
1108800
Other (OTH)
AF:
0.00
AC:
0
AN:
60180
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

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.81
CADD
Benign
0.19
DANN
Benign
0.76
PhyloP100
-0.64

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs775320200; hg19: chr2-26680902; API