3-52404535-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PM2PP2BP4
The NM_004656.4(BAP1):c.1168C>A(p.Pro390Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,776 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar 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 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.1168C>A | p.Pro390Thr | missense_variant | Exon 12 of 17 | ENST00000460680.6 | NP_004647.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.1168C>A | p.Pro390Thr | missense_variant | Exon 12 of 17 | 1 | NM_004656.4 | ENSP00000417132.1 | ||
BAP1 | ENST00000296288.9 | c.1114C>A | p.Pro372Thr | missense_variant | Exon 12 of 17 | 5 | ENSP00000296288.5 | |||
BAP1 | ENST00000490804.1 | n.596C>A | non_coding_transcript_exon_variant | Exon 2 of 3 | 2 | |||||
BAP1 | ENST00000469613.5 | c.-60C>A | upstream_gene_variant | 1 | ENSP00000418320.1 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248020Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134548
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461776Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727182
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
BAP1-related tumor predisposition syndrome Uncertain:2
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This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 390 of the BAP1 protein (p.Pro390Thr). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 490775). 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) performed at Invitae indicates that this missense variant is not expected to disrupt BAP1 protein function with a negative predictive value of 80%. 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:2
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The p.P390T variant (also known as c.1168C>A), located in coding exon 12 of the BAP1 gene, results from a C to A substitution at nucleotide position 1168. The proline at codon 390 is replaced by threonine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at