rs149596527
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_024685.4(BBS10):āc.1276A>Gā(p.Lys426Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000576 in 1,614,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K426R) has been classified as Uncertain significance.
Frequency
Consequence
NM_024685.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS10 | NM_024685.4 | c.1276A>G | p.Lys426Glu | missense_variant | 2/2 | ENST00000650064.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS10 | ENST00000650064.2 | c.1276A>G | p.Lys426Glu | missense_variant | 2/2 | NM_024685.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000394 AC: 60AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000876 AC: 22AN: 251264Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135802
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461828Hom.: 0 Cov.: 33 AF XY: 0.0000179 AC XY: 13AN XY: 727212
GnomAD4 genome ? AF: 0.000407 AC: 62AN: 152346Hom.: 0 Cov.: 32 AF XY: 0.000456 AC XY: 34AN XY: 74500
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome 10 Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Oct 28, 2019 | - - |
Bardet-Biedl syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 24, 2022 | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 426 of the BBS10 protein (p.Lys426Glu). This variant is present in population databases (rs149596527, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with BBS10-related conditions. ClinVar contains an entry for this variant (Variation ID: 406220). 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 BBS10 protein function. 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. - |
BBS10-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 30, 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at