rs767221160
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PM2PP5_Moderate
The NM_152384.3(BBS5):c.177G>A(p.Trp59Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,459,426 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
Genomes: not found (cov: 32)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
BBS5
NM_152384.3 stop_gained
NM_152384.3 stop_gained
Scores
5
1
1
Clinical Significance
Conservation
PhyloP100: 7.55
Genes affected
BBS5 (HGNC:970): (Bardet-Biedl syndrome 5) This gene encodes a protein that has been directly linked to Bardet-Biedl syndrome. The primary features of this syndrome include retinal dystrophy, obesity, polydactyly, renal abnormalities and learning disabilities. Experimentation in non-human eukaryotes suggests that this gene is expressed in ciliated cells and that it is required for the formation of cilia. Alternate transcriptional splice variants have been observed but have not been fully characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 12 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 2-169487103-G-A is Pathogenic according to our data. Variant chr2-169487103-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 6160.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-169487103-G-A is described in Lovd as [Likely_pathogenic].
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS5 | NM_152384.3 | c.177G>A | p.Trp59Ter | stop_gained | 3/12 | ENST00000295240.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS5 | ENST00000295240.8 | c.177G>A | p.Trp59Ter | stop_gained | 3/12 | 1 | NM_152384.3 | P1 | |
BBS5 | ENST00000392663.6 | c.177G>A | p.Trp59Ter | stop_gained | 3/11 | 1 | |||
BBS5 | ENST00000443151.1 | c.143-884G>A | intron_variant, NMD_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251076Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135726
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1459426Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6AN XY: 726162
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GnomAD4 genome ? Cov.: 32
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ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Bardet-Biedl syndrome 5 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | May 14, 2004 | - - |
Bardet-Biedl syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Feb 10, 2023 | This sequence change creates a premature translational stop signal (p.Trp59*) in the BBS5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS5 are known to be pathogenic (PMID: 15137946, 16877420, 26325687, 27708425, 28041643, 29806606). This variant is present in population databases (no rsID available, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 15137946). ClinVar contains an entry for this variant (Variation ID: 6160). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
MutationTaster
Benign
A;A;A
Vest4
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at