chr22-38729523-C-T
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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):c.1778C>T(p.Ser593Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000218 in 1,609,018 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 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000021 ( 0 hom. )
Consequence
GTPBP1
NM_004286.5 missense
NM_004286.5 missense
Scores
1
6
12
Clinical Significance
Conservation
PhyloP100: 7.53
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=0.21987388).
BS2
High AC in GnomAd4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GTPBP1 | NM_004286.5 | c.1778C>T | p.Ser593Leu | missense_variant | 11/12 | ENST00000216044.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GTPBP1 | ENST00000216044.10 | c.1778C>T | p.Ser593Leu | missense_variant | 11/12 | 1 | NM_004286.5 | P1 | |
GTPBP1 | ENST00000458073.5 | c.512C>T | p.Ser171Leu | missense_variant | 4/8 | 5 | |||
GTPBP1 | ENST00000462332.1 | n.1268C>T | non_coding_transcript_exon_variant | 1/2 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152108Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245554Hom.: 0 AF XY: 0.00000752 AC XY: 1AN XY: 133026
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GnomAD4 exome AF: 0.0000206 AC: 30AN: 1456910Hom.: 0 Cov.: 31 AF XY: 0.0000152 AC XY: 11AN XY: 724878
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GnomAD4 genome AF: 0.0000329 AC: 5AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74284
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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 | Apr 08, 2024 | The c.1778C>T (p.S593L) alteration is located in exon 11 (coding exon 11) of the GTPBP1 gene. This alteration results from a C to T substitution at nucleotide position 1778, causing the serine (S) at amino acid position 593 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
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.
Eigen
Uncertain
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;D
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
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