rs1553645164
Variant summary
Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_004656.4(BAP1):c.1153C>T(p.Arg385Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,512 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. R385R) has been classified as Likely benign. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_004656.4 stop_gained
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Pathogenic. Variant got 18 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.1153C>T | p.Arg385Ter | stop_gained | 12/17 | ENST00000460680.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.1153C>T | p.Arg385Ter | stop_gained | 12/17 | 1 | NM_004656.4 | P1 | |
BAP1 | ENST00000296288.9 | c.1099C>T | p.Arg367Ter | stop_gained | 12/17 | 5 | |||
BAP1 | ENST00000490804.1 | n.581C>T | non_coding_transcript_exon_variant | 2/3 | 2 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461512Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 727064
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
BAP1-related tumor predisposition syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Oct 17, 2023 | This sequence change creates a premature translational stop signal (p.Arg385*) in the BAP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BAP1 are known to be pathogenic (PMID: 21874000, 23684012). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with mesothelioma, cutaneous melanoma and/or uveal melanoma (PMID: 22545102, 25974357, 27181379). ClinVar contains an entry for this variant (Variation ID: 485271). For these reasons, this variant has been classified as Pathogenic. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 29, 2020 | The p.R385* pathogenic mutation (also known as c.1153C>T), located in coding exon 12 of the BAP1 gene, results from a C to T substitution at nucleotide position 1153. This changes the amino acid from an arginine to a stop codon within coding exon 12. This mutation has been shown to segregate with disease in a family with several BAP1-associated tumors including cutaneous melanoma, ocular melanoma, and atypical melanocytic nevi (Njauw CN et al. PLoS ONE. 2012;7(4):e35295). The p.R385* mutation has also been reported in an individual diagnosed with a meningioma, multiple cutaneous melanomas, as well as meosothelioma (Betti M et al. Cancer Lett. 2016 08;378:120-30). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at