Variant chr22-38706038-C-T 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_004286.5(GTPBP1):c.83C>T(p.Ala28Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000814 in 1,227,868 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.1e-7 ( 0 hom. )

Consequence

GTPBP1
NM_004286.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.988

Variant links:

Genes affected

GTPBP1 (HGNC:4669): (GTP binding protein 1) This gene is upregulated by interferon-gamma and encodes a protein that is a member of the AGP11/GTPBP1 family of GTP-binding proteins. A structurally similar protein has been found in mouse, where disruption of the gene for that protein had no observable phenotype. [provided by RefSeq, Jul 2008]

GTPBP1 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=0.11038986).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GTPBP1	NM_004286.5 linkuse as main transcript	c.83C>T	p.Ala28Val	missense_variant	1/12	ENST00000216044.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
GTPBP1	ENST00000216044.10 linkuse as main transcript	c.83C>T	p.Ala28Val	missense_variant	1/12	1	NM_004286.5	P1
GTPBP1	ENST00000484657.5 linkuse as main transcript	c.-52+221C>T		intron_variant		4
GTPBP1	ENST00000418601.1 linkuse as main transcript	c.83C>T	p.Ala28Val	missense_variant, NMD_transcript_variant	1/4	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.14e-7

AC:

AN:

1227868

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

599342

show subpopulations

Gnomad4 AFR exome

AF:

0.0000416

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jan 05, 2022

The c.83C>T (p.A28V) alteration is located in exon 1 (coding exon 1) of the GTPBP1 gene. This alteration results from a C to T substitution at nucleotide position 83, causing the alanine (A) at amino acid position 28 to be replaced by a valine (V). 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

0.098

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.21

FATHMM_MKL

Benign

0.42

LIST_S2

Benign

0.72

M_CAP

Benign

0.044

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.89

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.57

REVEL

Benign

0.081

Sift

Benign

0.16

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.22

MutPred

0.091

Gain of catalytic residue at A28 (P = 0.0558);

MVP

0.25

MPC

0.20

ClinPred

0.44

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.2

Varity_R

0.11

gMVP

0.22

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