22-38705978-C-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2

The NM_004286.5(GTPBP1):ā€‹c.23C>Gā€‹(p.Ser8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00004 in 1,448,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.00012 ( 0 hom., cov: 33)
Exomes š‘“: 0.000030 ( 0 hom. )

Consequence

GTPBP1
NM_004286.5 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM1
In a modified_residue Phosphoserine (size 0) in uniprot entity GTPB1_HUMAN
BP4
Computational evidence support a benign effect (MetaRNN=0.06884372).
BS2
High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GTPBP1NM_004286.5 linkuse as main transcriptc.23C>G p.Ser8Cys missense_variant 1/12 ENST00000216044.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GTPBP1ENST00000216044.10 linkuse as main transcriptc.23C>G p.Ser8Cys missense_variant 1/121 NM_004286.5 P1
GTPBP1ENST00000484657.5 linkuse as main transcriptc.-52+161C>G intron_variant 4
GTPBP1ENST00000418601.1 linkuse as main transcriptc.23C>G p.Ser8Cys missense_variant, NMD_transcript_variant 1/42

Frequencies

GnomAD3 genomes
AF:
0.000125
AC:
19
AN:
152218
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000314
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000770
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000489
AC:
4
AN:
81786
Hom.:
0
AF XY:
0.0000423
AC XY:
2
AN XY:
47280
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000365
Gnomad SAS exome
AF:
0.000120
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000301
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000301
AC:
39
AN:
1296542
Hom.:
0
Cov.:
30
AF XY:
0.0000282
AC XY:
18
AN XY:
637956
show subpopulations
Gnomad4 AFR exome
AF:
0.000377
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000211
Gnomad4 SAS exome
AF:
0.0000418
Gnomad4 FIN exome
AF:
0.0000617
Gnomad4 NFE exome
AF:
0.0000165
Gnomad4 OTH exome
AF:
0.0000189
GnomAD4 genome
AF:
0.000125
AC:
19
AN:
152332
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74484
show subpopulations
Gnomad4 AFR
AF:
0.000313
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000772
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000473
Bravo
AF:
0.0000945
ExAC
AF:
0.0000200
AC:
2
Asia WGS
AF:
0.00202
AC:
7
AN:
3478

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 submitterclinical testingAmbry GeneticsApr 08, 2024The c.23C>G (p.S8C) alteration is located in exon 1 (coding exon 1) of the GTPBP1 gene. This alteration results from a C to G substitution at nucleotide position 23, causing the serine (S) at amino acid position 8 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.081
BayesDel_addAF
Benign
-0.36
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
24
DANN
Uncertain
0.98
DEOGEN2
Benign
0.18
T
Eigen
Benign
-0.16
Eigen_PC
Benign
-0.018
FATHMM_MKL
Benign
0.43
N
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.032
D
MetaRNN
Benign
0.069
T
MetaSVM
Benign
-0.99
T
MutationAssessor
Benign
0.97
L
MutationTaster
Benign
0.63
N
PrimateAI
Uncertain
0.76
T
PROVEAN
Benign
-0.96
N
REVEL
Benign
0.057
Sift
Uncertain
0.010
D
Sift4G
Uncertain
0.031
D
Polyphen
0.0
B
Vest4
0.31
MutPred
0.10
Loss of phosphorylation at S8 (P = 0.004);
MVP
0.14
MPC
0.24
ClinPred
0.12
T
GERP RS
3.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.1
Varity_R
0.20
gMVP
0.50

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs745793999; hg19: chr22-39101983; API