19-17337646-C-A

Variant names:

Variant summary

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

The NM_032620.4(GTPBP3):c.35C>A(p.Ala12Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000846 in 1,181,446 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. A12S) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 8.5e-7 ( 0 hom. )

Consequence

GTPBP3
NM_032620.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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=0.13295543).

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.35C>A	p.Ala12Glu	missense	Exon 1 of 9	NP_116009.2	Q969Y2-1
GTPBP3	NM_133644.4		c.35C>A	p.Ala12Glu	missense	Exon 1 of 8	NP_598399.2	Q969Y2-2
GTPBP3	NM_001128855.3		c.35C>A	p.Ala12Glu	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.35C>A	p.Ala12Glu	missense	Exon 1 of 9	ENSP00000313818.7	Q969Y2-1
GTPBP3	ENST00000600625.5	TSL:1	c.35C>A	p.Ala12Glu	missense	Exon 1 of 9	ENSP00000473150.1	Q969Y2-3
GTPBP3	ENST00000600610.5	TSL:1	n.35C>A		non_coding_transcript_exon	Exon 1 of 7	ENSP00000469008.1	M0QXA1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.46e-7

AC:

AN:

1181446

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

564622

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23506

American (AMR)

AF:

0.00

AC:

AN:

11084

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16164

East Asian (EAS)

AF:

0.00

AC:

AN:

28008

South Asian (SAS)

AF:

0.00

AC:

AN:

38540

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41954

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4802

European-Non Finnish (NFE)

AF:

0.00000103

AC:

AN:

969276

Other (OTH)

AF:

0.00

AC:

AN:

48112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

0.14

BayesDel_addAF

Benign

-0.097

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.049

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.30

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.74

M_CAP

Benign

0.014

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

PhyloP100

1.2

PROVEAN

Benign

-0.89

REVEL

Benign

0.15

Sift

Uncertain

0.023

Sift4G

Uncertain

0.017

Polyphen

0.024

Vest4

0.37

MutPred

0.22

Gain of solvent accessibility (P = 0.0411)

MVP

0.36

MPC

0.35

ClinPred

0.70

GERP RS

2.5

PromoterAI

-0.014

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.15

gMVP

0.60

Mutation Taster

=89/11

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over