rs951076425
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_004656.4(BAP1):c.1522C>T(p.Arg508Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,718 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R508H) has been classified as Uncertain significance.
Frequency
Consequence
NM_004656.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.1522C>T | p.Arg508Cys | missense_variant | 13/17 | ENST00000460680.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.1522C>T | p.Arg508Cys | missense_variant | 13/17 | 1 | NM_004656.4 | P1 | |
BAP1 | ENST00000478368.1 | c.25C>T | p.Arg9Cys | missense_variant | 1/5 | 1 | |||
BAP1 | ENST00000469613.5 | c.119+178C>T | intron_variant | 1 | |||||
BAP1 | ENST00000296288.9 | c.1468C>T | p.Arg490Cys | missense_variant | 13/17 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000399 AC: 1AN: 250832Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135708
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461718Hom.: 0 Cov.: 32 AF XY: 0.00000275 AC XY: 2AN XY: 727148
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
BAP1-related tumor predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 08, 2023 | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 508 of the BAP1 protein (p.Arg508Cys). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 539921). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BAP1 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. - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 08, 2023 | The p.R508C variant (also known as c.1522C>T), located in coding exon 13 of the BAP1 gene, results from a C to T substitution at nucleotide position 1522. The arginine at codon 508 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at