rs781174906
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_198428.3(BBS9):c.445C>T(p.Arg149Ter) variant causes a stop gained, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,452,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_198428.3 stop_gained, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS9 | NM_198428.3 | c.445C>T | p.Arg149Ter | stop_gained, splice_region_variant | 6/23 | ENST00000242067.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS9 | ENST00000242067.11 | c.445C>T | p.Arg149Ter | stop_gained, splice_region_variant | 6/23 | 1 | NM_198428.3 | P3 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250306Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135284
GnomAD4 exome AF: 0.00000620 AC: 9AN: 1452672Hom.: 0 Cov.: 29 AF XY: 0.0000111 AC XY: 8AN XY: 722838
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 9 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Genomic Research Center, Shahid Beheshti University of Medical Sciences | Dec 18, 2017 | - - |
Bardet-Biedl syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Jun 01, 2023 | This sequence change creates a premature translational stop signal (p.Arg149*) in the BBS9 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS9 are known to be pathogenic (PMID: 16380913, 20177705). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 523079). This premature translational stop signal has been observed in individual(s) with Bardet–Biedl syndrome (PMID: 33777945). This variant is present in population databases (rs781174906, gnomAD 0.003%). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at