3-112999498-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014170.4(GTPBP8):ā€‹c.719T>Gā€‹(p.Val240Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000161 in 1,550,228 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.000017 ( 0 hom. )

Consequence

GTPBP8
NM_014170.4 missense

Scores

1
10
8

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.88
Variant links:
Genes affected
GTPBP8 (HGNC:25007): (GTP binding protein 8 (putative)) Predicted to enable GTP binding activity and metal ion binding activity. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GTPBP8NM_014170.4 linkc.719T>G p.Val240Gly missense_variant 5/6 ENST00000383678.8 NP_054889.2 Q8N3Z3-1Q9P025
GTPBP8NM_138485.2 linkc.620T>G p.Val207Gly missense_variant 4/5 NP_612494.1 Q8N3Z3-2

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GTPBP8ENST00000383678.8 linkc.719T>G p.Val240Gly missense_variant 5/61 NM_014170.4 ENSP00000373176.2 Q8N3Z3-1

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152248
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000126
AC:
3
AN:
237528
Hom.:
0
AF XY:
0.0000156
AC XY:
2
AN XY:
128228
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:
0.0000272
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000172
AC:
24
AN:
1397980
Hom.:
0
Cov.:
23
AF XY:
0.0000115
AC XY:
8
AN XY:
694536
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:
0.0000215
Gnomad4 OTH exome
AF:
0.0000173
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152248
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74394
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
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:
0.0000282
Hom.:
0
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2

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 GeneticsDec 01, 2022The c.719T>G (p.V240G) alteration is located in exon 5 (coding exon 5) of the GTPBP8 gene. This alteration results from a T to G substitution at nucleotide position 719, causing the valine (V) at amino acid position 240 to be replaced by a glycine (G). 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
Uncertain
0.44
BayesDel_addAF
Uncertain
0.046
T
BayesDel_noAF
Benign
-0.10
CADD
Uncertain
25
DANN
Uncertain
0.99
DEOGEN2
Benign
0.095
T;.;T;.;T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.60
FATHMM_MKL
Uncertain
0.92
D
LIST_S2
Benign
0.77
T;.;T;T;T
M_CAP
Benign
0.040
D
MetaRNN
Uncertain
0.50
T;T;T;T;T
MetaSVM
Uncertain
-0.24
T
MutationAssessor
Uncertain
2.8
M;.;.;.;.
PrimateAI
Benign
0.43
T
PROVEAN
Pathogenic
-4.7
D;D;.;D;D
REVEL
Benign
0.28
Sift
Uncertain
0.010
D;D;.;D;D
Sift4G
Benign
0.061
T;D;D;D;D
Polyphen
0.96
P;D;.;.;.
Vest4
0.36
MutPred
0.77
Loss of stability (P = 0.0075);.;.;.;.;
MVP
0.67
MPC
0.28
ClinPred
0.86
D
GERP RS
5.8
Varity_R
0.26
gMVP
0.70

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: rs767861476; hg19: chr3-112718345; API