rs767068756
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP5BP4
The NM_152618.3(BBS12):āc.1055A>Cā(p.Gln352Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000308 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_152618.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS12 | NM_152618.3 | c.1055A>C | p.Gln352Pro | missense_variant | 2/2 | ENST00000314218.8 | |
BBS12 | NM_001178007.2 | c.1055A>C | p.Gln352Pro | missense_variant | 3/3 | ||
BBS12 | XM_011531680.3 | c.1055A>C | p.Gln352Pro | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS12 | ENST00000314218.8 | c.1055A>C | p.Gln352Pro | missense_variant | 2/2 | 1 | NM_152618.3 | P1 | |
BBS12 | ENST00000542236.5 | c.1055A>C | p.Gln352Pro | missense_variant | 3/3 | 2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.0000478 AC: 12AN: 251302Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135832
GnomAD4 exome AF: 0.0000308 AC: 45AN: 1461840Hom.: 0 Cov.: 31 AF XY: 0.0000536 AC XY: 39AN XY: 727214
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 12 Pathogenic:1Uncertain:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Baylor Genetics | Dec 08, 2023 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | Sep 01, 2016 | - - |
Bardet-Biedl syndrome Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 06, 2022 | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 352 of the BBS12 protein (p.Gln352Pro). This variant is present in population databases (rs767068756, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 30614526). ClinVar contains an entry for this variant (Variation ID: 560429). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Pathogenic, no assertion criteria provided | provider interpretation | Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University | Sep 15, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Apr 12, 2021 | Variant summary: BBS12 c.1055A>C (p.Gln352Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 251302 control chromosomes, predominantly at a frequency of 0.00039 within the South Asian subpopulation in the gnomAD database. This frequency is somewhat lower than the maximum expected for a pathogenic variant in BBS12 causing Bardet-Biedl Syndrome (0.00076), allowing no conclusion about variant significance. The variant, c.1055A>C, has been reported in the literature in at least two apparently homozygous individuals with clinical features of Bardet-Biedl syndrome (Haer-Wigman_2017, Mary_2019). These data indicate that the variant maybe associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic (n=1) or VUS (n=2). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at