chr22-38729552-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.1807G>A​(p.Asp603Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000748 in 1,604,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

GTPBP1
NM_004286.5 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.92
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 -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.16974077).
BS2
High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GTPBP1NM_004286.5 linkuse as main transcriptc.1807G>A p.Asp603Asn missense_variant 11/12 ENST00000216044.10

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GTPBP1ENST00000216044.10 linkuse as main transcriptc.1807G>A p.Asp603Asn missense_variant 11/121 NM_004286.5 P1
GTPBP1ENST00000458073.5 linkuse as main transcriptc.541G>A p.Asp181Asn missense_variant 4/85
GTPBP1ENST00000462332.1 linkuse as main transcriptn.1297G>A non_coding_transcript_exon_variant 1/22

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152120
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000655
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000418
AC:
1
AN:
239108
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
129884
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000925
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000620
AC:
9
AN:
1452336
Hom.:
0
Cov.:
31
AF XY:
0.00000277
AC XY:
2
AN XY:
722476
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.03e-7
Gnomad4 OTH exome
AF:
0.000133
GnomAD4 genome
AF:
0.0000197
AC:
3
AN:
152120
Hom.:
0
Cov.:
33
AF XY:
0.0000269
AC XY:
2
AN XY:
74296
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.0000655
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.00000824
AC:
1

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 22, 2024The c.1807G>A (p.D603N) alteration is located in exon 11 (coding exon 11) of the GTPBP1 gene. This alteration results from a G to A substitution at nucleotide position 1807, causing the aspartic acid (D) at amino acid position 603 to be replaced by an asparagine (N). 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
0.12
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.58
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.13
T;.
Eigen
Benign
0.15
Eigen_PC
Uncertain
0.33
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.0078
T
MetaRNN
Benign
0.17
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.2
L;.
MutationTaster
Benign
1.0
D
PrimateAI
Benign
0.43
T
PROVEAN
Benign
0.63
N;N
REVEL
Benign
0.14
Sift
Benign
0.11
T;D
Sift4G
Benign
0.47
T;T
Polyphen
0.15
B;.
Vest4
0.23
MutPred
0.063
Loss of ubiquitination at K601 (P = 0.0162);.;
MVP
0.39
MPC
0.020
ClinPred
0.35
T
GERP RS
5.3
Varity_R
0.12
gMVP
0.17

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: rs777206173; hg19: chr22-39125557; API