chr11-64284391-T-C
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Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032989.3(BAD):c.-8-15A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000206 in 1,459,716 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 (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
BAD
NM_032989.3 splice_polypyrimidine_tract, intron
NM_032989.3 splice_polypyrimidine_tract, intron
Scores
1
14
Clinical Significance
Conservation
PhyloP100: -1.06
Genes affected
BAD (HGNC:936): (BCL2 associated agonist of cell death) The protein encoded by this gene is a member of the BCL-2 family. BCL-2 family members are known to be regulators of programmed cell death. This protein positively regulates cell apoptosis by forming heterodimers with BCL-xL (B-cell lymphoma-extra large) and BCL-2, and reversing their death repressor activity. Proapoptotic activity of this protein is regulated through its phosphorylation. Protein kinases AKT and MAP kinase, as well as protein phosphatase calcineurin were found to be involved in the regulation of this protein. Alternative splicing of this gene results in two transcript variants which encode the same isoform. [provided by RefSeq, Dec 2019]
GPR137 (HGNC:24300): (G protein-coupled receptor 137) Predicted to be involved in several processes, including negative regulation of bone resorption; negative regulation of osteoclast differentiation; and positive regulation of TORC1 signaling. Located in lysosomal membrane. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.05523005).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
BAD | NM_032989.3 | c.-8-15A>G | splice_polypyrimidine_tract_variant, intron_variant | ENST00000309032.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
BAD | ENST00000309032.8 | c.-8-15A>G | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_032989.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 152150Hom.: 0 Cov.: 33 FAILED QC
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GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249610Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135356
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GnomAD4 exome AF: 0.0000206 AC: 30AN: 1459716Hom.: 0 Cov.: 33 AF XY: 0.0000207 AC XY: 15AN XY: 726292
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GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74326
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 16, 2021 | The c.25T>C (p.C9R) alteration is located in exon 1 (coding exon 1) of the GPR137 gene. This alteration results from a T to C substitution at nucleotide position 25, causing the cysteine (C) at amino acid position 9 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
N;N;N;N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at