chr3-52406839-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BS2_Supporting
The NM_004656.4(BAP1):c.649G>A(p.Ala217Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000706 in 1,557,014 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A217A) has been classified as Likely benign.
Frequency
Consequence
NM_004656.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAP1 | NM_004656.4 | c.649G>A | p.Ala217Thr | missense_variant | 8/17 | ENST00000460680.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAP1 | ENST00000460680.6 | c.649G>A | p.Ala217Thr | missense_variant | 8/17 | 1 | NM_004656.4 | P1 | |
BAP1 | ENST00000296288.9 | c.649G>A | p.Ala217Thr | missense_variant | 8/17 | 5 | |||
BAP1 | ENST00000471532.5 | n.364G>A | non_coding_transcript_exon_variant | 4/5 | 5 | ||||
BAP1 | ENST00000483984.5 | n.506G>A | non_coding_transcript_exon_variant | 7/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33
GnomAD4 exome AF: 0.00000641 AC: 9AN: 1404826Hom.: 0 Cov.: 32 AF XY: 0.00000288 AC XY: 2AN XY: 693518
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152188Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74352
ClinVar
Submissions by phenotype
BAP1-related tumor predisposition syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 12, 2023 | 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. 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. ClinVar contains an entry for this variant (Variation ID: 472711). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 217 of the BAP1 protein (p.Ala217Thr). - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 30, 2018 | The p.A217T variant (also known as c.649G>A), located in coding exon 8 of the BAP1 gene, results from a G to A substitution at nucleotide position 649. The alanine at codon 217 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
BAP1-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jan 03, 2024 | The BAP1 c.649G>A variant is predicted to result in the amino acid substitution p.Ala217Thr. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. This variant is interpreted with uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/472711/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at