rs772235333
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate
The NM_024649.5(BBS1):c.1178G>A(p.Arg393Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,613,830 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R393G) has been classified as Uncertain significance.
Frequency
Consequence
NM_024649.5 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS1 | NM_024649.5 | c.1178G>A | p.Arg393Gln | missense_variant, splice_region_variant | 12/17 | ENST00000318312.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS1 | ENST00000318312.12 | c.1178G>A | p.Arg393Gln | missense_variant, splice_region_variant | 12/17 | 1 | NM_024649.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251298Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135816
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461660Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727146
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152170Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 1 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jun 14, 2016 | - - |
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2021 | This sequence change replaces arginine with glutamine at codon 393 of the BBS1 protein (p.Arg393Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs772235333, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with BBS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 377001). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at