rs148374859
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PP3PP5_Very_Strong
The NM_024685.4(BBS10):c.273C>G(p.Cys91Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,610,448 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 (★★). Synonymous variant affecting the same amino acid position (i.e. CH91F?) has been classified as Pathogenic.
Frequency
Consequence
NM_024685.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BBS10 | NM_024685.4 | c.273C>G | p.Cys91Trp | missense_variant | 2/2 | ENST00000650064.2 | NP_078961.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BBS10 | ENST00000650064.2 | c.273C>G | p.Cys91Trp | missense_variant | 2/2 | NM_024685.4 | ENSP00000497413 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 151924Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000282 AC: 7AN: 248572Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134626
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1458524Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16AN XY: 725764
GnomAD4 genome AF: 0.0000395 AC: 6AN: 151924Hom.: 0 Cov.: 32 AF XY: 0.0000270 AC XY: 2AN XY: 74160
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 10 Pathogenic:6
Pathogenic, no assertion criteria provided | literature only | OMIM | Dec 01, 2010 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 04, 2021 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München | Jan 29, 2020 | - - |
Pathogenic, no assertion criteria provided | clinical testing | Natera, Inc. | Sep 16, 2020 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Mar 17, 2024 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 17, 2022 | - - |
not provided Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jan 01, 2023 | BBS10: PM3:Strong, PP1:Strong, PM2 - |
Pathogenic, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 30, 2018 | - - |
Bardet-Biedl syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 23, 2023 | This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 91 of the BBS10 protein (p.Cys91Trp). This variant is present in population databases (rs148374859, gnomAD 0.006%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 16582908, 17980398, 19190184, 20472660, 20805367). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 30818). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BBS10 protein function. Experimental studies have shown that this missense change affects BBS10 function (PMID: 20498079). For these reasons, this variant has been classified as Pathogenic. - |
Pathogenic, no assertion criteria provided | provider interpretation | Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University | Sep 15, 2018 | - - |
Bardet-Biedl syndrome 1 Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Advanced Center For Translational And Genetic Medicine, Ann & Robert H. Lurie Children's Hospital Of Chicago | May 10, 2023 | - - |
Retinal dystrophy Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg | Jan 01, 2022 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at