chr1-89010998-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PP3_StrongBS2
The NM_018284.3(GBP3):c.1268G>A(p.Gly423Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000178 in 1,461,572 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000072 ( 0 hom., cov: 26)
Exomes 𝑓: 0.000019 ( 7 hom. )
Consequence
GBP3
NM_018284.3 missense
NM_018284.3 missense
Scores
3
7
9
Clinical Significance
Conservation
PhyloP100: 5.46
Genes affected
GBP3 (HGNC:4184): (guanylate binding protein 3) This gene encodes a member of the guanylate-binding protein (GBP) family. GBPs specifically bind guanine nucleotides (GMP, GDP, and GTP) and contain two of the three consensus motifs found in typical GTP-binding proteins. The encoded protein interacts with a member of the germinal center kinase family. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PP3
MetaRNN computational evidence supports a deleterious effect, 0.981
BS2
High Homozygotes in GnomAdExome4 at 7 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GBP3 | NM_018284.3 | c.1268G>A | p.Gly423Glu | missense_variant | 8/11 | ENST00000370481.9 | NP_060754.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GBP3 | ENST00000370481.9 | c.1268G>A | p.Gly423Glu | missense_variant | 8/11 | 1 | NM_018284.3 | ENSP00000359512.4 |
Frequencies
GnomAD3 genomes AF: 0.00000721 AC: 1AN: 138776Hom.: 0 Cov.: 26
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GnomAD3 exomes AF: 0.0000173 AC: 4AN: 231848Hom.: 1 AF XY: 0.0000160 AC XY: 2AN XY: 124952
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GnomAD4 exome AF: 0.0000189 AC: 25AN: 1322796Hom.: 7 Cov.: 31 AF XY: 0.0000197 AC XY: 13AN XY: 658636
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GnomAD4 genome AF: 0.00000721 AC: 1AN: 138776Hom.: 0 Cov.: 26 AF XY: 0.0000148 AC XY: 1AN XY: 67624
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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 | Jun 18, 2021 | The c.1268G>A (p.G423E) alteration is located in exon 8 (coding exon 7) of the GBP3 gene. This alteration results from a G to A substitution at nucleotide position 1268, causing the glycine (G) at amino acid position 423 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Pathogenic
D
MetaSVM
Benign
T
MutationAssessor
Pathogenic
H
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MutPred
Loss of catalytic residue at A422 (P = 0.0319);
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