rs149362446
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_ModerateBP6BS1
The NM_198428.3(BBS9):c.2105C>A(p.Thr702Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000123 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T702T) has been classified as Likely benign.
Frequency
Consequence
NM_198428.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS9 | NM_198428.3 | c.2105C>A | p.Thr702Asn | missense_variant | 19/23 | ENST00000242067.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS9 | ENST00000242067.11 | c.2105C>A | p.Thr702Asn | missense_variant | 19/23 | 1 | NM_198428.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000703 AC: 107AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000215 AC: 54AN: 251438Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135894
GnomAD4 exome AF: 0.0000616 AC: 90AN: 1461820Hom.: 1 Cov.: 31 AF XY: 0.0000591 AC XY: 43AN XY: 727216
GnomAD4 genome ? AF: 0.000709 AC: 108AN: 152282Hom.: 0 Cov.: 32 AF XY: 0.000618 AC XY: 46AN XY: 74462
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Jun 13, 2022 | DNA sequence analysis of the BBS9 gene demonstrated a sequence change, c.2105C>A, in exon 19 that results in an amino acid change, p.Thr702Asn. This sequence change has been described in the gnomAD database with a frequency of 0.24% in the African/African American subpopulation (dbSNP rs149362446). The p.Thr702Asn change affects a highly conserved amino acid residue located in a domain of the BBS9 protein that is not known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Thr702Asn substitution. This sequence change does not appear to have been previously described in individuals with BBS9-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Thr702Asn change remains unknown at this time. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 29, 2018 | - - |
BBS9-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 25, 2020 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Bardet-Biedl syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at