GeneBe

rs761709265

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_004286.5(GTPBP1):​c.1565C>G​(p.Ala522Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GTPBP1
NM_004286.5 missense

Scores

7
9
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.77

Publications

0 publications found
Variant links:
Genes affected
GTPBP1 (HGNC:4669): (GTP binding protein 1) This gene is upregulated by interferon-gamma and encodes a protein that is a member of the AGP11/GTPBP1 family of GTP-binding proteins. A structurally similar protein has been found in mouse, where disruption of the gene for that protein had no observable phenotype. [provided by RefSeq, Jul 2008]
GTPBP1 Gene-Disease associations (from GenCC):
  • neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1
    Inheritance: AR Classification: MODERATE Submitted by: G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.817

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004286.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GTPBP1
NM_004286.5
MANE Select
c.1565C>Gp.Ala522Gly
missense
Exon 10 of 12NP_004277.2O00178

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
GTPBP1
ENST00000216044.10
TSL:1 MANE Select
c.1565C>Gp.Ala522Gly
missense
Exon 10 of 12ENSP00000216044.5O00178
GTPBP1
ENST00000870601.1
c.1616C>Gp.Ala539Gly
missense
Exon 11 of 13ENSP00000540660.1
GTPBP1
ENST00000870603.1
c.1589C>Gp.Ala530Gly
missense
Exon 10 of 12ENSP00000540662.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD2 exomes
AF:
0.00000398
AC:
1
AN:
250956
AF XY:
0.00000737
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

ClinVar submissions as Germline
Significance:Uncertain significance
Revision:criteria provided, single submitter
View on ClinVar
Pathogenic
VUS
Benign
Condition
-
1
-
not specified (1)

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.86
BayesDel_addAF
Uncertain
0.091
D
BayesDel_noAF
Uncertain
-0.020
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.65
D
Eigen
Pathogenic
0.86
Eigen_PC
Pathogenic
0.84
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Benign
0.011
T
MetaRNN
Pathogenic
0.82
D
MetaSVM
Benign
-0.67
T
MutationAssessor
Uncertain
2.7
M
PhyloP100
7.8
PrimateAI
Pathogenic
0.87
D
PROVEAN
Uncertain
-3.9
D
REVEL
Uncertain
0.46
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.012
D
Polyphen
1.0
D
Vest4
0.76
MutPred
0.62
Loss of stability (P = 0.0987)
MVP
0.42
MPC
2.3
ClinPred
0.96
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.55
gMVP
0.88
Mutation Taster
=19/81
disease causing

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

Other links and lift over

dbSNP: rs761709265; hg19: chr22-39124015; API