12-75490511-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate
The NM_006851.3(GLIPR1):c.526G>A(p.Gly176Arg) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 25)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
GLIPR1
NM_006851.3 missense
NM_006851.3 missense
Scores
6
9
4
Clinical Significance
Conservation
PhyloP100: 8.40
Genes affected
GLIPR1 (HGNC:17001): (GLI pathogenesis related 1) This gene encodes a protein with similarity to both the pathogenesis-related protein (PR) superfamily and the cysteine-rich secretory protein (CRISP) family. Increased expression of this gene is associated with myelomocytic differentiation in macrophage and decreased expression of this gene through gene methylation is associated with prostate cancer. The protein has proapoptotic activities in prostate and bladder cancer cells. This gene is a member of a cluster on chromosome 12 containing two other similar genes. Alternatively spliced variants which encode different protein isoforms have been described; however, not all variants have been fully characterized. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.874
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLIPR1 | NM_006851.3 | c.526G>A | p.Gly176Arg | missense_variant | 3/6 | ENST00000266659.8 | NP_006842.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLIPR1 | ENST00000266659.8 | c.526G>A | p.Gly176Arg | missense_variant | 3/6 | 1 | NM_006851.3 | ENSP00000266659.3 | ||
GLIPR1 | ENST00000456650.7 | c.597G>A | p.Thr199Thr | synonymous_variant | 4/6 | 1 | ENSP00000391144.3 | |||
GLIPR1 | ENST00000550491.1 | c.174G>A | p.Thr58Thr | synonymous_variant | 3/4 | 3 | ENSP00000448008.1 | |||
GLIPR1 | ENST00000536703.5 | n.421-5066G>A | intron_variant | 2 | ENSP00000440595.1 |
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 130840Hom.: 0 Cov.: 25 FAILED QC
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GnomAD3 exomes AF: 0.00000405 AC: 1AN: 246736Hom.: 0 AF XY: 0.00000748 AC XY: 1AN XY: 133736
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GnomAD4 exome AF: 0.00000266 AC: 3AN: 1126536Hom.: 0 Cov.: 20 AF XY: 0.00000351 AC XY: 2AN XY: 569564
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GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 130840Hom.: 0 Cov.: 25 AF XY: 0.00 AC XY: 0AN XY: 61588
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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 | Feb 22, 2023 | The c.526G>A (p.G176R) alteration is located in exon 3 (coding exon 3) of the GLIPR1 gene. This alteration results from a G to A substitution at nucleotide position 526, causing the glycine (G) at amino acid position 176 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Gain of methylation at G176 (P = 0.0367);
MVP
MPC
ClinPred
D
GERP RS
Varity_R
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