22-38729478-A-C
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004286.5(GTPBP1):āc.1733A>Cā(p.Asn578Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000174 in 1,606,128 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 (ā ).
Frequency
Genomes: š 0.000039 ( 0 hom., cov: 32)
Exomes š: 0.000015 ( 0 hom. )
Consequence
GTPBP1
NM_004286.5 missense
NM_004286.5 missense
Scores
1
5
13
Clinical Significance
Conservation
PhyloP100: 8.85
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=0.22265613).
BS2
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GTPBP1 | NM_004286.5 | c.1733A>C | p.Asn578Thr | missense_variant | 11/12 | ENST00000216044.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTPBP1 | ENST00000216044.10 | c.1733A>C | p.Asn578Thr | missense_variant | 11/12 | 1 | NM_004286.5 | P1 | |
GTPBP1 | ENST00000458073.5 | c.467A>C | p.Asn156Thr | missense_variant | 4/8 | 5 | |||
GTPBP1 | ENST00000462332.1 | n.1223A>C | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000123 AC: 3AN: 243696Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132230
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GnomAD4 exome AF: 0.0000151 AC: 22AN: 1453986Hom.: 0 Cov.: 31 AF XY: 0.0000166 AC XY: 12AN XY: 723502
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GnomAD4 genome AF: 0.0000394 AC: 6AN: 152142Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74330
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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 28, 2023 | The c.1733A>C (p.N578T) alteration is located in exon 11 (coding exon 11) of the GTPBP1 gene. This alteration results from a A to C substitution at nucleotide position 1733, causing the asparagine (N) at amino acid position 578 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
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