chr22-38706077-G-T

Variant summary

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

The NM_004286.5(GTPBP1):​c.122G>T​(p.Gly41Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

GTPBP1
NM_004286.5 missense

Scores

1
1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.906
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]

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=0.09228593).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GTPBP1NM_004286.5 linkuse as main transcriptc.122G>T p.Gly41Val missense_variant 1/12 ENST00000216044.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GTPBP1ENST00000216044.10 linkuse as main transcriptc.122G>T p.Gly41Val missense_variant 1/121 NM_004286.5 P1
GTPBP1ENST00000484657.5 linkuse as main transcriptc.-52+260G>T intron_variant 4
GTPBP1ENST00000418601.1 linkuse as main transcriptc.122G>T p.Gly41Val missense_variant, NMD_transcript_variant 1/42
GTPBP1ENST00000461428.1 linkuse as main transcript upstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1207752
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
587550
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

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 submitterclinical testingAmbry GeneticsApr 23, 2024The c.122G>T (p.G41V) alteration is located in exon 1 (coding exon 1) of the GTPBP1 gene. This alteration results from a G to T substitution at nucleotide position 122, causing the glycine (G) at amino acid position 41 to be replaced by a valine (V). 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
0.081
BayesDel_addAF
Benign
-0.21
T
BayesDel_noAF
Benign
-0.55
CADD
Benign
20
DANN
Benign
0.97
DEOGEN2
Benign
0.12
T
Eigen
Benign
-0.73
Eigen_PC
Benign
-0.60
FATHMM_MKL
Benign
0.25
N
LIST_S2
Benign
0.76
T
M_CAP
Uncertain
0.12
D
MetaRNN
Benign
0.092
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.69
N
MutationTaster
Benign
0.95
D
PrimateAI
Pathogenic
0.88
D
PROVEAN
Benign
-0.18
N
REVEL
Benign
0.066
Sift
Benign
0.14
T
Sift4G
Benign
0.37
T
Polyphen
0.0040
B
Vest4
0.076
MutPred
0.12
Loss of methylation at R37 (P = 0.1062);
MVP
0.19
MPC
0.25
ClinPred
0.071
T
GERP RS
-2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.063
gMVP
0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr22-39102082; API