chr8-91071244-TAGAG-T
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_016023.5(OTUD6B):c.192_195del(p.Glu65AsnfsTer5) variant causes a frameshift change. The variant allele was found at a frequency of 0.0000143 in 1,613,614 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R64R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_016023.5 frameshift
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
OTUD6B | NM_016023.5 | c.192_195del | p.Glu65AsnfsTer5 | frameshift_variant | 2/7 | ENST00000404789.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
OTUD6B | ENST00000404789.8 | c.192_195del | p.Glu65AsnfsTer5 | frameshift_variant | 2/7 | 1 | NM_016023.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251044Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135684
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461538Hom.: 0 AF XY: 0.00000963 AC XY: 7AN XY: 727060
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152076Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74278
ClinVar
Submissions by phenotype
Intellectual developmental disorder with dysmorphic facies, seizures, and distal limb anomalies Pathogenic:3
Pathogenic, criteria provided, single submitter | clinical testing | 3billion | Jan 03, 2022 | Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000016, PM2_M). Patient’s phenotype is considered compatible with OTUD6B-related disorder (PP4_P). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. - |
Likely pathogenic, criteria provided, single submitter | clinical testing | Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center | Mar 22, 2023 | PVS1, PM2 - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at