chr22-38730652-G-A
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004286.5(GTPBP1):c.1958G>A(p.Arg653His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000722 in 1,605,922 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000071 ( 0 hom. )
Consequence
GTPBP1
NM_004286.5 missense
NM_004286.5 missense
Scores
5
5
9
Clinical Significance
Conservation
PhyloP100: 8.54
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 Likely_benign. Variant got -6 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.21047735).
BS2
?
High AC in GnomAd at 13 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GTPBP1 | NM_004286.5 | c.1958G>A | p.Arg653His | missense_variant | 12/12 | ENST00000216044.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTPBP1 | ENST00000216044.10 | c.1958G>A | p.Arg653His | missense_variant | 12/12 | 1 | NM_004286.5 | P1 | |
GTPBP1 | ENST00000458073.5 | c.692G>A | p.Arg231His | missense_variant | 5/8 | 5 | |||
GTPBP1 | ENST00000462332.1 | n.1448G>A | non_coding_transcript_exon_variant | 2/2 | 2 | ||||
GTPBP1 | ENST00000484971.1 | c.41G>A | p.Arg14His | missense_variant, NMD_transcript_variant | 1/4 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152130Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000902 AC: 22AN: 243784Hom.: 0 AF XY: 0.000113 AC XY: 15AN XY: 132470
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GnomAD4 exome AF: 0.0000708 AC: 103AN: 1453792Hom.: 0 Cov.: 29 AF XY: 0.0000760 AC XY: 55AN XY: 723562
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GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74312
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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 | Aug 17, 2022 | The c.1958G>A (p.R653H) alteration is located in exon 12 (coding exon 12) of the GTPBP1 gene. This alteration results from a G to A substitution at nucleotide position 1958, causing the arginine (R) at amino acid position 653 to be replaced by a histidine (H). 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
Pathogenic
DEOGEN2
Benign
T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;.
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
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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