Variant 22-38727324-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004286.5(GTPBP1):c.1513A>C(p.Ile505Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,435,606 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GTPBP1
NM_004286.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.08

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTPBP1	NM_004286.5 linkuse as main transcript	c.1513A>C	p.Ile505Leu	missense_variant	9/12	ENST00000216044.10	NP_004277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GTPBP1	ENST00000216044.10 linkuse as main transcript	c.1513A>C	p.Ile505Leu	missense_variant	9/12	1	NM_004286.5	ENSP00000216044	P1
GTPBP1	ENST00000458073.5 linkuse as main transcript	c.247A>C	p.Ile83Leu	missense_variant	2/8	5		ENSP00000388147

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000877

AC:

AN:

228148

Hom.:

AF XY:

0.00000805

AC XY:

AN XY:

124252

show subpopulations

Gnomad AFR exome

AF:

0.000139

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:

0.00000139

AC:

AN:

1435606

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

713594

show subpopulations

Gnomad4 AFR exome

AF:

0.0000313

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:

9.10e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Jul 09, 2021

The c.1513A>C (p.I505L) alteration is located in exon 9 (coding exon 9) of the GTPBP1 gene. This alteration results from a A to C substitution at nucleotide position 1513, causing the isoleucine (I) at amino acid position 505 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

0.76

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.11

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.30

T;.

Eigen

Pathogenic

0.73

Eigen_PC

Pathogenic

0.67

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.027

MetaRNN

Uncertain

0.50

D;D

MetaSVM

Benign

-0.53

MutationAssessor

Uncertain

2.5

M;.

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.26

Sift

Uncertain

0.023

D;D

Sift4G

Benign

0.11

T;T

Polyphen

0.99

D;.

Vest4

0.77

MutPred

0.48

Loss of catalytic residue at P507 (P = 0.0303);.;

MVP

0.13

MPC

2.2

ClinPred

0.82

GERP RS

5.1

Varity_R

0.30

gMVP

0.88

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