rs1235128564

Variant summary

Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PVS1PS1_ModeratePM2

The NM_032620.4(GTPBP3):​c.1A>C​(p.Met1?) variant causes a initiator codon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000171 in 1,172,294 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 0.0000017 ( 0 hom. )

Consequence

GTPBP3
NM_032620.4 initiator_codon

Scores

3
3
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.57
Variant links:
Genes affected
GTPBP3 (HGNC:14880): (GTP binding protein 3, mitochondrial) This locus encodes a GTP-binding protein. The encoded protein is localized to the mitochondria and may play a role in mitochondrial tRNA modification. Polymorphisms at this locus may be associated with severity of aminoglycoside-induced deafness, a disease associated with a mutation in the 12S rRNA. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Sep 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Pathogenic. Variant got 12 ACMG points.

PVS1
Start lost variant, next in-frame start position is after 39 pathogenic variants. Next in-frame start position is after 335 codons. Genomic position: 17341072. Lost 0.678 part of the original CDS.
PS1
Another start lost variant in NM_032620.4 (GTPBP3) was described as [Pathogenic] in ClinVar as 488854
PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GTPBP3NM_032620.4 linkc.1A>C p.Met1? initiator_codon_variant Exon 1 of 9 ENST00000324894.13 NP_116009.2 Q969Y2-1
GTPBP3NM_133644.4 linkc.1A>C p.Met1? initiator_codon_variant Exon 1 of 8 NP_598399.2 Q969Y2-2B7Z563
GTPBP3NM_001128855.3 linkc.1A>C p.Met1? initiator_codon_variant Exon 1 of 9 NP_001122327.1 Q969Y2-3B7Z563
GTPBP3NM_001195422.1 linkc.120-396A>C intron_variant Intron 1 of 8 NP_001182351.1 Q969Y2-4B7Z563

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GTPBP3ENST00000324894.13 linkc.1A>C p.Met1? initiator_codon_variant Exon 1 of 9 1 NM_032620.4 ENSP00000313818.7 Q969Y2-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000171
AC:
2
AN:
1172294
Hom.:
0
Cov.:
30
AF XY:
0.00000357
AC XY:
2
AN XY:
559654
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000359
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000104
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.20
D
BayesDel_noAF
Uncertain
0.060
CADD
Benign
21
DANN
Benign
0.92
DEOGEN2
Benign
0.032
T;.;.
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.016
FATHMM_MKL
Benign
0.55
D
LIST_S2
Uncertain
0.90
D;D;D
M_CAP
Uncertain
0.28
D
MetaRNN
Pathogenic
0.96
D;D;D
MetaSVM
Benign
-1.1
T
PROVEAN
Benign
-0.46
N;N;.
REVEL
Benign
0.25
Sift
Benign
0.22
T;T;.
Sift4G
Pathogenic
0.0
D;D;D
Polyphen
0.0010
B;B;B
Vest4
0.85
MutPred
0.98
Loss of disorder (P = 0.3353);Loss of disorder (P = 0.3353);Loss of disorder (P = 0.3353);
MVP
0.31
ClinPred
0.99
D
GERP RS
3.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.56
gMVP
0.37

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr19-17448421; API