rs150040166
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152618.3(BBS12):āc.787T>Cā(p.Tyr263His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. Y263Y) has been classified as Likely benign.
Frequency
Consequence
NM_152618.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS12 | NM_152618.3 | c.787T>C | p.Tyr263His | missense_variant | 2/2 | ENST00000314218.8 | |
BBS12 | NM_001178007.2 | c.787T>C | p.Tyr263His | missense_variant | 3/3 | ||
BBS12 | XM_011531680.3 | c.787T>C | p.Tyr263His | missense_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS12 | ENST00000314218.8 | c.787T>C | p.Tyr263His | missense_variant | 2/2 | 1 | NM_152618.3 | P1 | |
BBS12 | ENST00000542236.5 | c.787T>C | p.Tyr263His | missense_variant | 3/3 | 2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000125 AC: 19AN: 152208Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251364Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135856
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461884Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727242
GnomAD4 genome ? AF: 0.000125 AC: 19AN: 152326Hom.: 0 Cov.: 33 AF XY: 0.0000805 AC XY: 6AN XY: 74488
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 12 Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Counsyl | Feb 22, 2017 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Apr 19, 2022 | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Feb 06, 2020 | - - |
BBS12-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 11, 2024 | The BBS12 c.787T>C variant is predicted to result in the amino acid substitution p.Tyr263His. This variant was previously reported as an additional variant in a patient who presented with Bardet-Biedl syndrome; however, that individual already carried plausible causative variants in BBS10 (Billingsley et al. 2010. PubMed ID: 20472660). This variant is reported in 0.056% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 263 of the BBS12 protein (p.Tyr263His). This variant is present in population databases (rs150040166, gnomAD 0.05%). This missense change has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 20472660). ClinVar contains an entry for this variant (Variation ID: 550824). 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) performed at Invitae indicates that this missense variant is not expected to disrupt BBS12 protein function with a negative predictive value of 80%. 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