rs878855171
Variant summary
Our verdict is Uncertain significance. The variant received 5 ACMG points: 5P and 0B. PM1PM2PP3
The NM_001122955.4(BSCL2):c.505C>T(p.Pro169Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000657 in 152,128 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 Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P169L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001122955.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Our verdict: Uncertain_significance. The variant received 5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BSCL2 | NM_001122955.4 | c.505C>T | p.Pro169Ser | missense_variant | Exon 4 of 11 | ENST00000360796.10 | NP_001116427.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BSCL2 | ENST00000360796.10 | c.505C>T | p.Pro169Ser | missense_variant | Exon 4 of 11 | 1 | NM_001122955.4 | ENSP00000354032.5 | ||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*556C>T | non_coding_transcript_exon_variant | Exon 17 of 24 | 2 | ENSP00000456010.1 | ||||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*556C>T | 3_prime_UTR_variant | Exon 17 of 24 | 2 | ENSP00000456010.1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 30 show subpopulations
GnomAD4 exome Cov.: 32
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152128Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 74306 show subpopulations
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
In summary, this is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C25"). This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a BSCL2-related disease. This sequence change replaces proline with serine at codon 105 of the BSCL2 protein (p.Pro105Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at