20-17494129-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001195.5(BFSP1):c.1943C>T(p.Thr648Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001195.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BFSP1 | ENST00000377873.8 | c.1943C>T | p.Thr648Ile | missense_variant | Exon 8 of 8 | 1 | NM_001195.5 | ENSP00000367104.3 | ||
BFSP1 | ENST00000377868.6 | c.1568C>T | p.Thr523Ile | missense_variant | Exon 8 of 8 | 1 | ENSP00000367099.2 | |||
BFSP1 | ENST00000536626.7 | c.1526C>T | p.Thr509Ile | missense_variant | Exon 9 of 9 | 2 | ENSP00000442522.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251314Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135832
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461788Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 727188
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Cataract 33 Uncertain:1
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: "Probably Damaging"; Align-GVGD: "Class C0"). 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. This variant has not been reported in the literature in individuals with BFSP1-related conditions. This sequence change replaces threonine with isoleucine at codon 648 of the BFSP1 protein (p.Thr648Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs752902567, ExAC 0.03%). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at