rs137852837
Variant summary
Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PM2PP3PP5_Very_Strong
The NM_024685.4(BBS10):c.931T>G(p.Ser311Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S311F) has been classified as Uncertain significance.
Frequency
Consequence
NM_024685.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BBS10 | NM_024685.4 | c.931T>G | p.Ser311Ala | missense_variant | 2/2 | ENST00000650064.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BBS10 | ENST00000650064.2 | c.931T>G | p.Ser311Ala | missense_variant | 2/2 | NM_024685.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461014Hom.: 0 Cov.: 33 AF XY: 0.00000138 AC XY: 1AN XY: 726880
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Bardet-Biedl syndrome Pathogenic:2
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | May 05, 2022 | For these reasons, this variant has been classified as Pathogenic. This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 311 of the BBS10 protein (p.Ser311Ala). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 16823392, 26518167). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1331). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). Experimental studies have shown that this missense change affects BBS10 function (PMID: 20080638). - |
Pathogenic, no assertion criteria provided | clinical testing | Sydney Genome Diagnostics, Children's Hospital Westmead | May 30, 2018 | This patient is homozygous for the c.931T>G (p.Ser311Ala) variant in the BBS10 gene. This variant has been previously described in a large extended family with multiple individuals with Bardet-Biedl syndrome (Laurier et al. 2006. Eur J Hum Genet 14:1195-1203; Stoetzel et al. 2006 Nat Genet 38:521-524). This variant is considered to be pathogenic according to the ACMG guidelines. Homozygous or compound heterozygous mutations in BBS10 are associated with Bardet-Biedl syndrome-10 (OMIM #615987). The mode of inheritance is autosomal recessive. - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jun 01, 2019 | - - |
Bardet-Biedl syndrome 10 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 2006 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at