chr22-38726286-C-T
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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):c.1247C>T(p.Thr416Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,882 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
GTPBP1
NM_004286.5 missense
NM_004286.5 missense
Scores
1
8
10
Clinical Significance
Conservation
PhyloP100: 6.14
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.1247C>T | p.Thr416Ile | missense_variant | 8/12 | ENST00000216044.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTPBP1 | ENST00000216044.10 | c.1247C>T | p.Thr416Ile | missense_variant | 8/12 | 1 | NM_004286.5 | P1 | |
GTPBP1 | ENST00000460605.1 | n.439C>T | non_coding_transcript_exon_variant | 3/3 | 3 | ||||
GTPBP1 | ENST00000475959.1 | n.373C>T | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
GTPBP1 | ENST00000458073.5 | upstream_gene_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251318Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135850
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461872Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 727238
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GnomAD4 genome AF: 0.00000658 AC: 1AN: 152010Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74264
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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 25, 2023 | The c.1247C>T (p.T416I) alteration is located in exon 8 (coding exon 8) of the GTPBP1 gene. This alteration results from a C to T substitution at nucleotide position 1247, causing the threonine (T) at amino acid position 416 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Uncertain
D
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
Sift4G
Benign
T
Polyphen
P
Vest4
MutPred
Loss of methylation at R418 (P = 0.1339);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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