22-38727324-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004286.5(GTPBP1):ā€‹c.1513A>Cā€‹(p.Ile505Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,435,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

GTPBP1
NM_004286.5 missense

Scores

4
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.08
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 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GTPBP1NM_004286.5 linkuse as main transcriptc.1513A>C p.Ile505Leu missense_variant 9/12 ENST00000216044.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GTPBP1ENST00000216044.10 linkuse as main transcriptc.1513A>C p.Ile505Leu missense_variant 9/121 NM_004286.5 P1
GTPBP1ENST00000458073.5 linkuse as main transcriptc.247A>C p.Ile83Leu missense_variant 2/85

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000877
AC:
2
AN:
228148
Hom.:
0
AF XY:
0.00000805
AC XY:
1
AN XY:
124252
show subpopulations
Gnomad AFR exome
AF:
0.000139
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000139
AC:
2
AN:
1435606
Hom.:
0
Cov.:
31
AF XY:
0.00000280
AC XY:
2
AN XY:
713594
show subpopulations
Gnomad4 AFR exome
AF:
0.0000313
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:
9.10e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 GeneticsJul 09, 2021The c.1513A>C (p.I505L) alteration is located in exon 9 (coding exon 9) of the GTPBP1 gene. This alteration results from a A to C substitution at nucleotide position 1513, causing the isoleucine (I) at amino acid position 505 to be replaced by a leucine (L). 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
Pathogenic
0.76
BayesDel_addAF
Benign
-0.091
T
BayesDel_noAF
Benign
-0.11
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.30
T;.
Eigen
Pathogenic
0.73
Eigen_PC
Pathogenic
0.67
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.97
D;D
M_CAP
Benign
0.027
D
MetaRNN
Uncertain
0.50
D;D
MetaSVM
Benign
-0.53
T
MutationAssessor
Uncertain
2.5
M;.
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.79
T
PROVEAN
Benign
-1.8
N;N
REVEL
Benign
0.26
Sift
Uncertain
0.023
D;D
Sift4G
Benign
0.11
T;T
Polyphen
0.99
D;.
Vest4
0.77
MutPred
0.48
Loss of catalytic residue at P507 (P = 0.0303);.;
MVP
0.13
MPC
2.2
ClinPred
0.82
D
GERP RS
5.1
Varity_R
0.30
gMVP
0.88

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: rs760618071; hg19: chr22-39123329; API