rs769048111
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001122955.4(BSCL2):c.1369C>T(p.Pro457Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001122955.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BSCL2 | NM_001122955.4 | c.1369C>T | p.Pro457Ser | missense_variant | Exon 11 of 11 | ENST00000360796.10 | NP_001116427.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BSCL2 | ENST00000360796.10 | c.1369C>T | p.Pro457Ser | missense_variant | Exon 11 of 11 | 1 | NM_001122955.4 | ENSP00000354032.5 | ||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*1420C>T | non_coding_transcript_exon_variant | Exon 24 of 24 | 2 | ENSP00000456010.1 | ||||
HNRNPUL2-BSCL2 | ENST00000403734.2 | n.*1420C>T | 3_prime_UTR_variant | Exon 24 of 24 | 2 | ENSP00000456010.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251402Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135878
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461786Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6AN XY: 727202
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Charcot-Marie-Tooth disease type 2 Uncertain:1
This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 393 of the BSCL2 protein (p.Pro393Ser). This variant is present in population databases (rs769048111, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BSCL2-related conditions. ClinVar contains an entry for this variant (Variation ID: 806685). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at