Variant 22-38705978-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2

The NM_004286.5(GTPBP1):c.23C>G(p.Ser8Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00004 in 1,448,874 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000030 ( 0 hom. )

Consequence

GTPBP1
NM_004286.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.20

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 -4 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity GTPB1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.06884372).

BS2

High AC in GnomAd4 at 19 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GTPBP1	NM_004286.5 linkuse as main transcript	c.23C>G	p.Ser8Cys	missense_variant	1/12	ENST00000216044.10	NP_004277.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GTPBP1	ENST00000216044.10 linkuse as main transcript	c.23C>G	p.Ser8Cys	missense_variant	1/12	1	NM_004286.5	ENSP00000216044	P1
GTPBP1	ENST00000484657.5 linkuse as main transcript	c.-52+161C>G		intron_variant		4		ENSP00000442881
GTPBP1	ENST00000418601.1 linkuse as main transcript	c.23C>G	p.Ser8Cys	missense_variant, NMD_transcript_variant	1/4	2		ENSP00000397891

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.0000489

AC:

AN:

81786

Hom.:

AF XY:

0.0000423

AC XY:

AN XY:

47280

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000365

Gnomad SAS exome

AF:

0.000120

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000301

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000301

AC:

AN:

1296542

Hom.:

Cov.:

AF XY:

0.0000282

AC XY:

AN XY:

637956

show subpopulations

Gnomad4 AFR exome

AF:

0.000377

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000211

Gnomad4 SAS exome

AF:

0.0000418

Gnomad4 FIN exome

AF:

0.0000617

Gnomad4 NFE exome

AF:

0.0000165

Gnomad4 OTH exome

AF:

0.0000189

GnomAD4 genome

AF:

0.000125

AC:

AN:

152332

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74484

show subpopulations

Gnomad4 AFR

AF:

0.000313

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.0000945

ExAC

AF:

0.0000200

AC:

Asia WGS

AF:

0.00202

AC:

AN:

3478

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 08, 2024

The c.23C>G (p.S8C) 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 23, causing the serine (S) at amino acid position 8 to be replaced by a cysteine (C). 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

0.081

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.44

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.18

Eigen

Benign

-0.16

Eigen_PC

Benign

-0.018

FATHMM_MKL

Benign

0.43

LIST_S2

Benign

0.73

M_CAP

Benign

0.032

MetaRNN

Benign

0.069

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.97

MutationTaster

Benign

0.63

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-0.96

REVEL

Benign

0.057

Sift

Uncertain

0.010

Sift4G

Uncertain

0.031

Polyphen

0.0

Vest4

0.31

MutPred

0.10

Loss of phosphorylation at S8 (P = 0.004);

MVP

0.14

MPC

0.24

ClinPred

0.12

GERP RS

3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.20

gMVP

0.50

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