Genetic Variant GTPBP1:p.Asp11Glu (chr22-38705988-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_004286.5(GTPBP1):c.33C>G(p.Asp11Glu) 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. 14/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

GTPBP1
NM_004286.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.459

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:

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=0.05469221).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTPBP1	NM_004286.5 link	c.33C>G	p.Asp11Glu	missense_variant	Exon 1 of 12	ENST00000216044.10	NP_004277.2	O00178

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GTPBP1	ENST00000216044.10 link	c.33C>G	p.Asp11Glu	missense_variant	Exon 1 of 12	1	NM_004286.5	ENSP00000216044.5	O00178
GTPBP1	ENST00000484657.5 link	c.-52+171C>G		intron_variant	Intron 1 of 3	4		ENSP00000442881.1	F5H716
GTPBP1	ENST00000418601.1 link	n.33C>G		non_coding_transcript_exon_variant	Exon 1 of 4	2		ENSP00000397891.1	F8WAZ4
GTPBP1	ENST00000461428.1 link	n.-130C>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1305112

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

641978

Gnomad4 AFR exome

AF:

0.00

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.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 10, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.33C>G (p.D11E) alteration is located in exon 1 (coding exon 1) of the GTPBP1 gene. This alteration results from a C to G substitution at nucleotide position 33, causing the aspartic acid (D) at amino acid position 11 to be replaced by a glutamic acid (E). 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

0.083

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.12

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.18

LIST_S2

Benign

0.57

M_CAP

Benign

0.026

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.26

PrimateAI

Uncertain

0.75

PROVEAN

Benign

0.050

REVEL

Benign

0.11

Sift

Benign

0.60

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.089

MutPred

0.063

Loss of MoRF binding (P = 0.0817);

MVP

0.12

MPC

0.18

ClinPred

0.11

GERP RS

1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.053

gMVP

0.11

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over