Genetic Variant GTPBP3:p.Gly4Val (chr19-17337622-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032620.4(GTPBP3):c.11G>T(p.Gly4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G4R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GTPBP3
NM_032620.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.00400

Publications

0 publications found

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]

GTPBP3 Gene-Disease associations (from GenCC):

combined oxidative phosphorylation defect type 23
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
mitochondrial disease
Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
Leigh syndrome
Inheritance: AR Classification: MODERATE Submitted by: ClinGen

GTPBP3 links:

ENSG00000307319 (HGNC:):

ENSG00000307319 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07838309).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032620.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTPBP3	NM_032620.4	MANE Select	c.11G>T	p.Gly4Val	missense	Exon 1 of 9	NP_116009.2	Q969Y2-1
GTPBP3	NM_133644.4		c.11G>T	p.Gly4Val	missense	Exon 1 of 8	NP_598399.2	Q969Y2-2
GTPBP3	NM_001128855.3		c.11G>T	p.Gly4Val	missense	Exon 1 of 9	NP_001122327.1	Q969Y2-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTPBP3	ENST00000324894.13	TSL:1 MANE Select	c.11G>T	p.Gly4Val	missense	Exon 1 of 9	ENSP00000313818.7	Q969Y2-1
GTPBP3	ENST00000600625.5	TSL:1	c.11G>T	p.Gly4Val	missense	Exon 1 of 9	ENSP00000473150.1	Q969Y2-3
GTPBP3	ENST00000600610.5	TSL:1	n.11G>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000469008.1	M0QXA1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1177180

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

562200

African (AFR)

AF:

0.00

AC:

AN:

23468

American (AMR)

AF:

0.00

AC:

AN:

11152

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16052

East Asian (EAS)

AF:

0.00

AC:

AN:

27908

South Asian (SAS)

AF:

0.00

AC:

AN:

37388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4812

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

966560

Other (OTH)

AF:

0.00

AC:

AN:

47974

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

8.9

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.032

Eigen

Benign

-0.84

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.040

LIST_S2

Benign

0.64

M_CAP

Benign

0.0040

MetaRNN

Benign

0.078

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.90

PhyloP100

0.0040

PROVEAN

Benign

-0.91

REVEL

Benign

0.15

Sift

Uncertain

0.018

Sift4G

Benign

0.11

Polyphen

0.74

Vest4

0.15

MutPred

0.45

Loss of disorder (P = 0.0053)

MVP

0.25

MPC

0.37

ClinPred

0.48

GERP RS

-1.9

PromoterAI

-0.14

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.045

gMVP

0.44

Mutation Taster

=77/23

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over