Variant 3-112995163-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_014170.4(GTPBP8):c.464A>G(p.Lys155Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000313 in 1,598,178 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 (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

GTPBP8
NM_014170.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.17

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]

GTPBP8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06279972).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTPBP8	NM_014170.4 linkuse as main transcript	c.464A>G	p.Lys155Arg	missense_variant	3/6	ENST00000383678.8	NP_054889.2	Q8N3Z3-1Q9P025
GTPBP8	NM_138485.2 linkuse as main transcript	c.365A>G	p.Lys122Arg	missense_variant	2/5		NP_612494.1	Q8N3Z3-2
GTPBP8	XM_047448046.1 linkuse as main transcript	c.436-1729A>G		intron_variant			XP_047304002.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTPBP8	ENST00000383678.8 linkuse as main transcript	c.464A>G	p.Lys155Arg	missense_variant	3/6	1	NM_014170.4	ENSP00000373176.2		Q8N3Z3-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000127

AC:

AN:

236628

Hom.:

AF XY:

0.00

AC XY:

AN XY:

127956

show subpopulations

Gnomad AFR exome

AF:

0.000188

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000277

AC:

AN:

1445962

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719368

show subpopulations

Gnomad4 AFR exome

AF:

0.0000615

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:

0.00000181

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0000241

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000491

ExAC

AF:

0.00000824

AC:

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 submitter

clinical testing

Ambry Genetics

Nov 10, 2022

The c.464A>G (p.K155R) alteration is located in exon 3 (coding exon 3) of the GTPBP8 gene. This alteration results from a A to G substitution at nucleotide position 464, causing the lysine (K) at amino acid position 155 to be replaced by an arginine (R). 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

0.068

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.62

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0015

T;.;T;.;T

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.22

FATHMM_MKL

Benign

0.74

LIST_S2

Benign

0.81

T;.;T;T;T

M_CAP

Benign

0.0039

MetaRNN

Benign

0.063

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.56

N;.;.;.;.

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.59

N;N;.;N;N

REVEL

Benign

0.042

Sift

Benign

0.23

T;T;.;T;T

Sift4G

Benign

0.41

T;T;T;T;T

Polyphen

0.097

B;B;.;.;.

Vest4

0.17

MutPred

0.47

Loss of methylation at K155 (P = 0.0016);.;.;.;.;

MVP

0.048

MPC

0.093

ClinPred

0.097

GERP RS

4.5

Varity_R

0.034

gMVP

0.51

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over