Variant chr3-113000887-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014170.4(GTPBP8):c.823T>C(p.Phe275Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000011 in 1,448,454 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

GTPBP8
NM_014170.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.91

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26334608).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTPBP8	NM_014170.4 linkuse as main transcript	c.823T>C	p.Phe275Leu	missense_variant	6/6	ENST00000383678.8	NP_054889.2	Q8N3Z3-1Q9P025
GTPBP8	NM_138485.2 linkuse as main transcript	c.724T>C	p.Phe242Leu	missense_variant	5/5		NP_612494.1	Q8N3Z3-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTPBP8	ENST00000383678.8 linkuse as main transcript	c.823T>C	p.Phe275Leu	missense_variant	6/6	1	NM_014170.4	ENSP00000373176.2		Q8N3Z3-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

249440

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

134836

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:

0.0000177

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.0000110

AC:

AN:

1448454

Hom.:

Cov.:

AF XY:

0.0000125

AC XY:

AN XY:

721392

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000450

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:

0.00000908

Gnomad4 OTH exome

AF:

0.0000501

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000450

Hom.:

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

Apr 12, 2022

The c.823T>C (p.F275L) alteration is located in exon 6 (coding exon 6) of the GTPBP8 gene. This alteration results from a T to C substitution at nucleotide position 823, causing the phenylalanine (F) at amino acid position 275 to be replaced by a leucine (L). 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

Pathogenic

0.95

BayesDel_addAF

Benign

-0.082

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.013

T;.;T;.;T

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.83

T;.;T;T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.26

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.18

N;.;.;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.6

D;D;.;D;D

REVEL

Benign

0.15

Sift

Benign

0.16

T;T;.;T;T

Sift4G

Benign

0.70

T;T;T;T;T

Polyphen

0.91

P;P;.;.;.

Vest4

0.46

MutPred

0.58

Loss of glycosylation at S278 (P = 0.0982);.;.;.;.;

MVP

0.20

MPC

0.36

ClinPred

0.56

GERP RS

5.6

Varity_R

0.27

gMVP

0.66

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.

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