Genetic Variant NM_004286.5:c.33C>G (chr22-38705988-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with characteristic facial and ectodermal features and tetraparesis 1
Inheritance: AR Classification: MODERATE Submitted by: G2P

GTPBP1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05469221).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004286.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GTPBP1	NM_004286.5	MANE Select	c.33C>G	p.Asp11Glu	missense	Exon 1 of 12	NP_004277.2	O00178

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTPBP1	ENST00000216044.10	TSL:1 MANE Select	c.33C>G	p.Asp11Glu	missense	Exon 1 of 12	ENSP00000216044.5	O00178
GTPBP1	ENST00000870601.1		c.33C>G	p.Asp11Glu	missense	Exon 1 of 13	ENSP00000540660.1
GTPBP1	ENST00000870603.1		c.33C>G	p.Asp11Glu	missense	Exon 1 of 12	ENSP00000540662.1

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

African (AFR)

AF:

0.00

AC:

AN:

26598

American (AMR)

AF:

0.00

AC:

AN:

27086

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22956

East Asian (EAS)

AF:

0.00

AC:

AN:

28778

South Asian (SAS)

AF:

0.00

AC:

AN:

73056

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4640

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1035894

Other (OTH)

AF:

0.00

AC:

AN:

53478

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.083

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

(source)

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

PhyloP100

0.46

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

PromoterAI

0.15

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.053

gMVP

0.11

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over