rs786204250
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM5PP3_Moderate
The NM_032043.3(BRIP1):c.2447G>T(p.Trp816Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. W816C) has been classified as Uncertain significance.
Frequency
Consequence
NM_032043.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BRIP1 | NM_032043.3 | c.2447G>T | p.Trp816Leu | missense_variant | 17/20 | ENST00000259008.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BRIP1 | ENST00000259008.7 | c.2447G>T | p.Trp816Leu | missense_variant | 17/20 | 1 | NM_032043.3 | P2 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 30
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 14, 2021 | DNA sequence analysis of the BRIP1 gene demonstrated a sequence change, c.2447G>T, in exon 17 that results in an amino acid change, p.Trp816Leu. This sequence change does not appear to have been previously described in individuals with BRIP1-related disorders and has also not been described in population databases such as ExAC and gnomAD. The p.Trp816Leu change affects a highly conserved amino acid residue located in a domain of the BRIP1 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Trp816Leu substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Trp816Leu change remains unknown at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.