2-26464878-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP6
The NM_194248.3(OTOF):c.4951G>A(p.Asp1651Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000181 in 1,602,912 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. D1651D) has been classified as Likely benign.
Frequency
Consequence
NM_194248.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTOF | NM_194248.3 | c.4951G>A | p.Asp1651Asn | missense_variant | 39/47 | ENST00000272371.7 | |
OTOF | NM_194323.3 | c.2650G>A | p.Asp884Asn | missense_variant | 22/29 | ENST00000339598.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTOF | ENST00000272371.7 | c.4951G>A | p.Asp1651Asn | missense_variant | 39/47 | 1 | NM_194248.3 | A1 | |
OTOF | ENST00000339598.8 | c.2650G>A | p.Asp884Asn | missense_variant | 22/29 | 1 | NM_194323.3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000164 AC: 4AN: 244374Hom.: 0 AF XY: 0.00000757 AC XY: 1AN XY: 132144
GnomAD4 exome AF: 0.00000965 AC: 14AN: 1450760Hom.: 0 Cov.: 31 AF XY: 0.00000693 AC XY: 5AN XY: 721038
GnomAD4 genome ? AF: 0.0000986 AC: 15AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74310
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 13, 2013 | The Asp1651Asn variant in OTOF has not been previously reported in individuals w ith hearing loss but was detected in 0.02% (1/4406) of African American chromoso mes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu; dbSNP r s139201321). Computational tools (amino acid biochemical properties, conservati on, AlignGVGD, SIFT, PolyPhen-2) do not provide strong evidence for or against a n impact to the protein. Additional information is required to establish the cl inical significance of this variant. - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 06, 2023 | The c.4951G>A (p.D1651N) alteration is located in exon 39 (coding exon 39) of the OTOF gene. This alteration results from a G to A substitution at nucleotide position 4951, causing the aspartic acid (D) at amino acid position 1651 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 05, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at