22-38727324-A-C
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004286.5(GTPBP1):āc.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
NM_004286.5 missense
Scores
4
6
9
Clinical Significance
Conservation
PhyloP100: 9.08
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]
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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 |
---|---|---|---|---|---|---|---|
GTPBP1 | NM_004286.5 | c.1513A>C | p.Ile505Leu | missense_variant | 9/12 | ENST00000216044.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTPBP1 | ENST00000216044.10 | c.1513A>C | p.Ile505Leu | missense_variant | 9/12 | 1 | NM_004286.5 | P1 | |
GTPBP1 | ENST00000458073.5 | c.247A>C | p.Ile83Leu | missense_variant | 2/8 | 5 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000877 AC: 2AN: 228148Hom.: 0 AF XY: 0.00000805 AC XY: 1AN XY: 124252
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GnomAD4 exome AF: 0.00000139 AC: 2AN: 1435606Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 2AN XY: 713594
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GnomAD4 genome Cov.: 32
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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 | Jul 09, 2021 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Benign
T;T
Polyphen
D;.
Vest4
MutPred
Loss of catalytic residue at P507 (P = 0.0303);.;
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