1-89264835-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_052942.5(GBP5):​c.1000G>A​(p.Asp334Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GBP5
NM_052942.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.441
Variant links:
Genes affected
GBP5 (HGNC:19895): (guanylate binding protein 5) This gene belongs to the TRAFAC class dynamin-like GTPase superfamily. The encoded protein acts as an activator of NLRP3 inflammasome assembly and has a role in innate immunity and inflammation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2017]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.21719587).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GBP5NM_052942.5 linkc.1000G>A p.Asp334Asn missense_variant Exon 8 of 12 ENST00000370459.8 NP_443174.1
GBP5NM_001134486.4 linkc.1000G>A p.Asp334Asn missense_variant Exon 7 of 11 NP_001127958.1
GBP5NM_001391920.1 linkc.1000G>A p.Asp334Asn missense_variant Exon 8 of 10 NP_001378849.1
LOC100421401 n.89264835C>T intragenic_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GBP5ENST00000370459.8 linkc.1000G>A p.Asp334Asn missense_variant Exon 8 of 12 5 NM_052942.5 ENSP00000359488.3 Q96PP8-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000119
AC:
3
AN:
251468
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135906
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000653
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461890
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000696
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000165
AC:
2

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Oct 07, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1000G>A (p.D334N) alteration is located in exon 8 (coding exon 6) of the GBP5 gene. This alteration results from a G to A substitution at nucleotide position 1000, causing the aspartic acid (D) at amino acid position 334 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.45
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
17
DANN
Uncertain
0.99
DEOGEN2
Benign
0.023
T;T
Eigen
Benign
-0.31
Eigen_PC
Benign
-0.30
FATHMM_MKL
Uncertain
0.80
D
LIST_S2
Benign
0.066
T;T
M_CAP
Benign
0.0046
T
MetaRNN
Benign
0.22
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.5
M;.
PrimateAI
Benign
0.35
T
PROVEAN
Uncertain
-3.6
D;D
REVEL
Benign
0.093
Sift
Benign
0.11
T;T
Sift4G
Benign
0.069
T;.
Polyphen
0.29
B;.
Vest4
0.31
MVP
0.29
ClinPred
0.57
D
GERP RS
3.1
Varity_R
0.11
gMVP
0.089

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs143883598; hg19: chr1-89730518; API